Variation of usual interstitial pneumonia using HRCT in Scleroderma Patients

Background:It is unknown whether patients with interstitial lung disease (ILD) and only some features of autoimmunity have a different natural history from those with a defined connective tissue disease (CTD-ILD). The classification criteria for “ILD with autoimmune features” (IPAF) may not be able to characterize all these patients, especially those with a usual interstitial pneumonia (UIP) pattern [1].Objectives:To determine clinical characteristics and predictive factors for progression in a cohort of ILD patients with features of autoimmunity, through the application of classification criteria for IPAF and specific CTD, whenever possible.Methods:We retrospectively selected a cohort of consecutive patients with ILD as onset manifestation and features of autoimmunity (at least 1 autoantibody and/or 1 clinical sign/symptom), evaluated by our multidisciplinary unit from March 2009 to March 2020. All the final diagnoses were revised according to the latest CTD and IPAF criteria. Patients were followed up for 33 (16.5-69.5) months.Results:Of the 101 patients enrolled (67.4±10.9 yrs, F/M ratio 65/36), 53 (52.5%) and 37 (36.6%) respectively satisfied the CTD and IPAF criteria. Eleven patients (10.9%) did not satisfy IPAF criteria because of only 1 item (clinical or serologic) within the IPAF domains and a UIP pattern; we defined this group as “autoimmune” UIP (AI-UIP). All the 8 patients initially classified as undifferentiated CTD had sufficient IPAF criteria. Among the IPAF patients (68.2±10.1 years, F/M ratio 20/17), the most common findings were: Nonspecific interstitial pneumonia pattern (56.8%), antinuclear antibodies positivity (43.2%) and arthritis (24.3%). The combination of a positive morphologic and serologic domain was the most common to reach the diagnosis (48.6%). Some IPAF patients had features not included in IPAF criteria, such as non-anti-synthetase myositis-specific antibodies (21.6%), objective sicca syndrome (13.5%) and anti-myeloperoxidase antibodies (2.7%). Over a median of 17 months, 2 IPAF patients (5.4%) developed a definite UIP pattern, while 4 (10.8%) a specific CTD. Comparing the IPAF, CTD-ILD and AI-UIP groups, no statistically significant differences were found in the mean age, sex distribution, smoking habits and mean duration of the disease. However, IPAF patients had a significantly higher prevalence of arterial hypertension and left-sided heart failure and a lower predominance of UIP pattern as expected (10.8% vs. 32.1% vs. 100%, p<0.01). Although no differences were found at the diagnosis, at 1 year the proportion of IPAF patients with radiological progression of the fibrosis and/or functional deterioration (defined by a decline in FVC of ≥ 10% and/or DLCO of ≥ 15% predicted) was lower to that of CTD-ILD and AI-UIP (17.1% vs. 31.4% vs. 63.6%, p 0.01). Fewer IPAF patients needed oxygen support (8.6% vs. 31.4% vs. 36.4, p 0.02). Considering the overall 101 patients, having an IPAF and a UIP pattern respectively predicted a slower (OR: 0.37, p 0.04) and a faster (OR: 3.56, p 0.01) ILD progression at the multivariate analysis.Conclusion:In our cohort, IPAF criteria were useful to identify a subset of patients with a slower ILD progression and a possible evolution to CTD (10-15% of cases) [2]. These criteria do not characterize all the patients with a UIP pattern and limited features of autoimmunity, which seem to have a worse prognosis, independently from the final diagnosis. Further studies are needed to clarify if the prognosis of AI-UIP is different from that of idiopathic pulmonary fibrosis.References:[1]Graney, et al. Ann Am Thorac Soc 2019;16(5):525-33.[2]Sebastiani, et al. Biomedicines 2021,9,17.Disclosure of Interests:None declared

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Interstitial Lung Disease and Anti-Myeloperoxidase Antibodies: Not a Simple Association

Journal of Clinical Medicine ◽

10.3390/jcm10122548 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2548

Author(s):

Marco Sebastiani ◽

Fabrizio Luppi ◽

Gianluca Sambataro ◽

Diego Castillo Villegas ◽

Stefania Cerri ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Rheumatic Disease ◽

Lung Disease ◽

Interstitial Pneumonia ◽

Usual Interstitial Pneumonia ◽

Clinical History ◽

High Resolution Computed Tomography ◽

Function Testing ◽

And Diffusion

Anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (MPO) antibodies, have been frequently identified in patients with idiopathic pulmonary fibrosis (IPF). However, their role remains unclear, and only 7–23% of these patients develops clinically overt vasculitis. We aimed to investigate the clinical, serological, and radiological features and prognosis of anti-MPO-positive interstitial lung disease (ILD) patients. Fifty-eight consecutive patients firstly referred for idiopathic interstitial pneumonia and showing serological positivity of anti-MPO antibodies were retrospectively enrolled. For each patient, clinical data, lung function testing, chest high-resolution computed tomography (HRCT) pattern, and survival were recorded. Thirteen patients developed a rheumatic disease during a median follow-up of 39 months. Usual interstitial pneumonia (UIP) was the most frequent ILD pattern, significantly influencing the patients’ survival. In fact, while the 52-week survival of the overall population was 71.4 ± 7.5%, significantly higher than IPF, survivals of anti-MPO patients with UIP pattern and IPF were similar. Forced vital capacity and diffusion lung capacity for CO significantly declined in 37.7 and 41.5% of cases, respectively, while disease progression at chest HRCT was observed in 45.2%. A careful clinical history and evaluation should always be performed in ILD patients with anti-MPO antibodies to quickly identify patients who are developing a systemic rheumatic disease.

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POS0875 MYOSITIS-SPECIFIC ANTIBODIES IN A RETROSPECTIVE SINGLE-CENTER OBSERVATIONAL STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3234 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 693.2-694

Author(s):

J. Álvarez Troncoso ◽

S. Carrasco Molina ◽

J. Valdivieso ◽

P. Nozal ◽

Á. Robles Marhuenda ◽

...

Keyword(s):

Risk Factors ◽

Observational Study ◽

Interstitial Pneumonia ◽

Usual Interstitial Pneumonia ◽

Older Age ◽

Single Center ◽

Specific Antibodies ◽

Factors Associated ◽

Risk Of Cancer ◽

Single Center Observational Study

Background:Myositis-specific antibodies (MSA) are highly specific and useful to classify patients as having syndromes with distinct clinical features and prognosis. MSA are almost always mutually exclusive and quite specific, adding value as a useful biomarker for diagnosis. Although individual autoantibodies aren’t sensitive enough to detect the full spectrum of idiopathic inflammatory myopathies (IIM), the sensitivity of a myositis panel is increasing as more autoantibodies are discovered, and as better assays become available.Objectives:We aimed to analyze the usefulness of a myositis-specific immunoblot for the diagnosis of IIM in a hospital cohort from January 2019 to December 2020. We also seek to correlate immunological findings with the risk of associated interstitial lung disease (ILD), cancer, or death.Methods:Retrospective single-center observational study conducted in a Spanish tertiary hospital. In patients with high clinical suspicion of IIM, a myositis immunoblot was performed including Jo1, PL-7, PL-12, EJ, SRP, Mi2, Ku, MDA-5, TIF1-γ, HMGCR, PM-Scl and Ro52 antibodies. The demographic characteristics, the risk of ILD, cancer and death were analyzed.Results:In a cohort of 313 patients with high suspicion of IIM, 87 patients (27.8%) presented a positive MSA (MSA+ve). The mean age at diagnosis was 56.7±16.9 years, with no significant differences between MSA+ve and MSA-ve (p=0.597). Most of the patients were women with significant differences between both groups (80.5% MSA+ve vs 68.1% MSA-ve, p=0.030).IIM were classified as antisynthetase syndrome (ARS) (38%), dermatomyositis (DM) (31%), overlap myopathy (OM) (16.9%) and necrotizing myopathy (NM) (14.1%) according to the manifestations and MSA found (Jo1, PL-12, PL-7, EJ in ARS; Mi-2, MDA-5 and TIF1-γ in DM; Ku and PM-Scl in OM; HMGCR and SRP in NM). The most frequent MSA were anti-Jo1 (16.9%), TIF1-γ (15.5%), Ku (12.7%), Mi-2 (9.9%), PL-7 (9.9%), HMCGR (8.5%), PL-12 (7%), MDA-5 (5.6%), SRP (5.6%) and EJ (4.2%). The presence of Ro52 associated with other MSA was found in 20 patients (22.9%).ILD was the most frequent manifestation (45.2% of the MSA+ve). Non-specific interstitial pneumonia (NSIP) was the most frequent ILD (39.5%), followed by usual interstitial pneumonia (34.2%). The main risk factors associated with IIM-ILD were some subtypes of the MSAs (p<0.001), the association of Ro52 (p<0.001), and older age (p=0.027). Among the IIM, ARS and OM (p<0.001) were more frequently associated with IIM-ILD. The MSAs most associated with IIM-ILD were Jo1, PL-7, PM-Scl, Ku and SRP (p<0.001).Cancer was found in 9.6% of MSA+ve patients. The most frequent tumors were gynecological (37.5%), followed by gastrointestinal (25%) and breast cancer (12.5%). Factors associated with cancer were age (p=0.010), TIF1-γ (p<0.001), SRP (p=0.004), PL-12 (p=0.013), PL-7 (p=0.047) and HMGCR (p=0.027).The mortality of these patients was 3.5%. There were no differences regarding MSA+ve/-ve (p = 0.911). However, MDA-5 (p=0.033) and older age (p=0.001) were associated with higher mortality. There were no significant differences between the IIM classifications, the associated SAD, the presence of cancer or ILD. However, longer follow-up periods and future studies are necessary to confirm these results.Conclusion:The use of a myositis blot allowed classifying, stratifying the risk of ILD, the risk of cancer and the risk of mortality in IIM. IIM-ILD was the most frequent complication, usually manifested as NSIP. The associated risk factors were ARS, OM, some MSAs, Ro52+ and older age. Cancer was a serious and frequent manifestation in these patients, especially in patients with TIF1-γ and other MSAs, so it is essential to know the risk factors and perform an early screening, especially in older patients.A better knowledge of the serological profiles of IIM will provide more individualized approaches and better risk stratification, helping in the management and treatment of these patients.References:[1]Satoh et al. Clin Rev Allergy Immunol. 2017 Feb;52(1):1-19.[2]Betteridge et al. J Intern Med. 2016 Jul;280(1):8-23.Disclosure of Interests:None declared

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SAT0529 CLINICAL CHARACTERISTICS AND TREATMENT PATTERNS IN A PATIENT GROUP WITH INTERSTITIAL LUNG DISEASE.

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5812 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1222.2-1222

Author(s):

R. Ortega Castro ◽

P. S. Laura ◽

F. U. Pilar ◽

J. Calvo Gutierrez ◽

A. Requejo-Jimenez ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Interstitial Pneumonia ◽

Smoking Habit ◽

Inflammatory Myopathy ◽

Usual Interstitial Pneumonia ◽

Treatment Patterns ◽

Common Symptom ◽

Radiological Pattern ◽

Mechanic’S Hands

Background:Diffuse interstitial lung disease (ILD) is frequently associated with connective tissue diseases (CTD) and is one of the main causes of morbidity and mortality in these patients. Recently, the concept of Interstitial Pneumonia with Autoimmune Features (IPAF) has been defined to characterize ILD associated with systemic manifestations limited to subtle serological and clinical autoimmune abnormalities and not fulfilling the international criteria for the diagnosis of a given CTD.Objectives:The objective of this study is to describe the clinical, serological and radiological characteristics, as well as the treatment patterns of patients with ILD referred to a Rheumatology Service for suspected CTDMethods:Observational, cross-sectional study of 43 patients with ILD referred for evaluation to the medical consultation of CTD of the Rheumatology service at the Reina Sofía Hospital. Patients were classified as patients with defined CTD, patient with IPAF and patients with other types of pneumopathy. We conducted a descriptive study of all patients and compared the clinical-analytical-radiological characteristics and treatment patterns of the first two groups.Results:Of the 43 patients, 67.40% were women with a mean age at diagnosis of 65.65 (10.42) years and 53.50% of smoking patientsOf the total of patients, 16 (37.2%) were included in the CTD group, 17 (39.5%) met criteria for IPAF and 10 (23.3%) had another type of pneumopathy.In the CTD group scleroderma was the most frequent disease (6/16), followed by inflammatory myopathy (4/16), Sjögren’s syndrome (3/16), rheumatoid arthritis (2/16) and polymyalgia rheumatic (1/16). In this group of patients, the most common symptom was Raynaud’s phenomenon (RP) (7/16), followed by arthritis (7/16) and mechanic’s hands (3/16). Regarding the most frequently antibodies were ANA (100%), anti-RO (41.7%), anti-citrullinated protein antibodies (30%) and rheumatoid factor (RF) (28.6%).In patients with IPAF, as in the CTD group, the most observed clinical criterion was RP (5/17), followed by arthritis (1/17) and mechanic’s hands (1/17). Among the serological criteria the most common antibodies were ANA (100%), followed by anti-RO (33.3%), anti-RNA synthetase (28.6%) and RF (22.2%).Regarding the radiological pattern, in both groups the most frequent was nonspecific interstitial pneumonia, followed by the indeterminate pattern and usual interstitial pneumonia (UIP) in third place. There were no significant differences by gender and age, between the group of CTD and IPAF, observing in both groups a predominance of women with a similar mean age, being the upper smoking habit in the IPAF group (70.6% vs 31.5%, p= 0.02). Regarding the treatment used, the use of immunosuppressants (IS) was more frequent in CTD group (56.3% vs 11.8%, p = 0.007).Conclusion:The clinical-serological and radiological characteristics were similar among patients with IPAF and CTD, which supports the notion of a similar pathophysiology in both groups. In our cohort patients with CTD received IS more frequently than IPAF group, however, future work would be necessary to assess whether the response to treatment is similar in these populations and if IS can benefit patients with IPAF to long term. In addition, it could be useful to include the UIP pattern within the IPAF classification criteria, not currently included, since it is the third most frequent radiological pattern.References:[1]Respirology, 21 (2016), pp. 245-258[2]Eur Respir J, 46 (2015), pp. 976-987Disclosure of Interests:Rafaela Ortega Castro: None declared, Pérez Sánchez Laura: None declared, Font Ugalde Pilar: None declared, Jerusalem Calvo Gutierrez: None declared, Antonio Requejo-Jimenez: None declared, Simona Espejo-Pérez: None declared, Teresa Gonzalez-Serrano: None declared, María del Carmen Castro Villegas: None declared, Gómez García Ignacio: None declared, Alejandro Escudero Contreras: None declared, Eduardo Collantes Estevez Grant/research support from: ROCHE and Pfizer, Speakers bureau: ROCHE, Lilly, Bristol and Celgene, Maria A Aguirre: None declared

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SAT0535 CLINICAL COURSE IN PATIENTS WITH INTERSTITIAL PNEUMONIA WITH AUTOIMMUNE FEATURES (IPAF) IN A MULTIDISCIPLINARY CONSULTATION.

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4607 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1225.1-1225

Author(s):

I. Perez ◽

C. Vadillo ◽

M. A. Nieto ◽

D. Freites ◽

Z. Rosales ◽

...

Keyword(s):

Incidence Rate ◽

Interstitial Pneumonia ◽

Usual Interstitial Pneumonia ◽

Classification Criteria ◽

Therapeutic Management ◽

European Respiratory Society ◽

Respiratory Impairment ◽

Radiological Pattern ◽

Over Time

Background:A proportion of patients with Interstitial Lung Disease (ILD) show autoimmune characteristics but do not completely meet the classification criteria for a definitive connective tissue disease. In order to unify the nomenclature and criteria to define this condition, the classification of patients with Interstitial Pneumonia with Autoimmune Features (IPAF) has recently been adopted (Fisher, et al).Objectives:To describe the sociodemographic, clinical, functional characteristics and therapeutic management of IPAF patients in clinical practice and to evaluate the incidence rate of functional respiratory impairment over time.Methods:A longitudinal observational study was performed. Patients with IPAF classification criteria (Fischer et al) were included from the time of ILD diagnosis (Feb 2017 to Sept 2018) and followed until loss of follow-up or end of the study (Oct 2019), in a multidisciplinary team, carried by a pneumologist and a rheumatologist in a Tertiary Hospital in Madrid. Main outcome: relative functional respiratory impairment: defined as decline in percent predicted forced vital capacity (FVC%) of ≥ 5% compared to the previous visit. Respiratory function was measured at baseline and every 6 months. Covariates: a) sociodemographic, b) clinical, c) radiological pattern (non-specific interstitial pneumonia [NSIP]; usual interstitial pneumonia [UIP], others); d) FVC%, DLCO%; e) laboratory tests; f) therapy used (glucorticosteroids, disease modifying antirheumatic drugs (DMARDs) and Biologic Agents). Statistical analysis: description of the sociodemographic, clinical, radiological, functional and treatment characteristics of the patients. Survival techniques were used to estimate the incidence rate (IR) of relative functional respiratory impairment, expressed per 100 patient-semester with their respective confidence interval [95 % CI].Results:17 patients were included with a mean follow-up of 3 ± 1.5 years, 70.6% were women with a mean age of 65±10 years. The most frequent IPAF classification criteria were: a) clinical: arthritis (50%), Raynaud`s phenomenon (33%) and mechanical hands (17%); b) serological: 65% had ANA ≥1/360; 31% FR> 40; 30% Anti-Ro positive; c) morphologic: 59% presented NSIP pattern and 29.4% was UIP. The baseline median FVC% and DLCO% were 89 [83-107.7] and 63 [50-79.8] respectively. During the study period, 94% received treatment: 87.5% glucorticosteroids, 68.5% mycophenolate, 56% azathioprine, 18.7% cyclophosphamide iv and 33% antifibrotics. During the follow-up (104.6 patient - semester), 15 patients presented relative functional respiratory impairment, with an IR of 23.8 [16.1-35.3]. After 14 months from IPAF diagnosis 50% of the patients had relative functional respiratory impairment. At the end of the follow-up, 50% showed a worsening of the DLCO%.Conclusion:IPAF patients are mostly women in their sixties. The most frequent clinical criteria are arthritis and Raynaud`s phenomenon and the serological were FR and ANAs. The most frequent radiological pattern was NSIP. The therapeutic management is mainly with glucorticosteroids, mycophenolate and azathioprine. At the beginning, patients have a slightly diminished lung function. These patients have significant functional impairment over time that will impact in their prognosis. Longitudinal and multicenter studies are necessary to advance in the knowledge and management of these patients.References:[1]Fischer A, Antoniou KM, Brown KK, Cadranel J, Corte TJ, du Bois RM, et al. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J [Internet]. 2015 Oct;46(4):976–87. Available from:http://www.ncbi.nlm.nih.gov/pubmed/26160873Disclosure of Interests:None declared

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The myositis clinical phenotype associated with anti-Zo autoantibodies: a case series of nine UK patients

Rheumatology ◽

10.1093/rheumatology/kez504 ◽

2019 ◽

Vol 59 (7) ◽

pp. 1626-1631 ◽

Cited By ~ 1

Author(s):

Sarah L Tansley ◽

Zoe Betteridge ◽

Hui Lu ◽

Emma Davies ◽

Simon Rothwell ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Interstitial Pneumonia ◽

Clinical Phenotype ◽

Disease Onset ◽

Usual Interstitial Pneumonia ◽

Trna Synthetase ◽

Muscle Disease ◽

Ancestral Haplotype ◽

Common Finding

Abstract Objectives It has been over 10 years since the first report of autoantibodies directed against phenylalanyl tRNA synthetase (anti-Zo) in a patient with features of the anti-synthetase syndrome. In that time no further cases have been published. Here we aim to characterize more fully the clinical phenotype of anti-Zo–associated myositis by describing the clinical features of nine patients. Methods Anti-Zo was identified by protein-immunoprecipitation in patients referred for extended spectrum myositis autoantibody testing at our laboratory. Results were confirmed by immunodepletion using a reference serum. Medical records were retrospectively reviewed to provide detailed information of the associated clinical phenotype for all identified patients. Where possible, HLA genotype was imputed using Illumina protocols. Results Nine patients with anti-Zo were identified. The median age at disease onset was 51 years, and six patients were female. Seven patients had evidence of inflammatory muscle disease, seven of interstitial lung disease and six of arthritis. The reported pattern of interstitial lung disease varied with usual interstitial pneumonia, non-specific interstitial pneumonia and organizing pneumonia all described. Other features of the anti-synthetase syndrome such as RP and mechanics hands were common. HLA data was available for three patients, all of whom had at least one copy of the HLA 8.1 ancestral haplotype. Conclusion Patients with anti-Zo presenting with features of the anti-synthetase syndrome and interstitial lung disease is a common finding. Like other myositis autoantibodies, there is likely to be a genetic association with the HLA 8.1 ancestral haplotype.

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