BackgroundHematological manifestations are common in systemic lupus erythematosus (SLE), and are thought to result from immune-mediated peripheral cell destruction or bone marrow failure(1,2).ObjectivesTo assess the clinical characteristics and outcomes of severe hematological disease in a large cohort of lupus patients.MethodsRetrospective analysis of the “Attikon” lupus cohort (over 800 patients total) (3) for the identification of patients with a history of severe hematological manifestation. The latter were defined as: thrombocytopenia with a platelet count <30.000/mm3, hemolytic anemia with an hemoglobin <8 g/dL, neutropenia with less than 500 neutrophils/mm3, history of thrombotic microangiopathy (TMA) or macrophage activation syndrome (MAS). Treatments and long-term outcomes (relapses, mortality) were recorded.ResultsAmong 300 patients with hematologic manifestations, 40 patients had severe disease. Most of them were women (75%). Mean age at SLE diagnosis was 41,1 years and mean disease duration at diagnosis of cytopenia was 3.8 years. Hematologic manifestation preceded SLE diagnosis in 13 patients (32,5%).Autoimmune thrombocytopenia was the most common (57,5%), followed by hemolytic anemia (17.5%), TMA (12.5%) and Evans syndrome (7,5%). All patients received glucocorticoids (GC). Rituximab (15%) and cyclophosphamide (12,5%) were the most frequently used GC-sparing agents during the first episode. Nine patients (22,5%) received intravenous immunoglobulin (IVIg). Relapse occurred in 23 patients (57,5%), most of which (N=17, 73,9%) were treated with GC alone or in combination with IVIg or plasma exchange at initial presentation, without the use of GC-sparing agents. Most of the flares (60,8%) were severe. No deaths were observed.ConclusionHematological disease in SLE is treatment-responsive. GC remain the mainstay of treatment, but the high relapse rates underscore the need for more efficient GC-sparing agents.References[1]Fayyaz A, Igoe A, Kurien BT, Danda D, James JA, Stafford HA, Scofield RH. Haematological manifestations of lupus. Lupus Sci Med. 2015 Mar 3;2(1):e000078.[2]Hepburn AL, Narat S, Mason JC. The management of peripheral blood cytopenias in systemic lupus erythematosus. Rheumatology (Oxford). 2010 Dec;49(12):2243-54[3]Nikolopoulos D, Kostopoulou M, Pieta A, Karageorgas T, Tseronis D, Chavatza K, Flouda S, Rapsomaniki P, Banos A, Kremasmenou E, Tzavara V, Katsimbri P, Fanouriakis A, Boumpas DT. Evolving phenotype of systemic lupus erythematosus in Caucasians: low incidence of lupus nephritis, high burden of neuropsychiatric disease and increased rates of late-onset lupus in the ‘Attikon’ cohort. Lupus. 2020 Apr;29(5):514-522.Table 1.Characteristics of patients with hematological manifestationsAge at diagnosis, mean (years)41,1Women N(%)30(75)Mean disease duration at cytopenia diagnosis (years)3,8Thrombocytopenia, N=23, (mean platelet count,/mm3)11682Hemolytic anemia,N=7 (mean Hb,g/dL)6,75Neutropenia N=1,(mean neutrophil count)450Evans syndrome, N=3 (mean Hb, g, mean platelet count)7 /46600TMA,N=5, (mean platelet count)8750MAS, N=1Immunosuppressive treatment at initial presentationAzathioprine (N,%) 4(10) Corticosteroids (N,%) 40 (100) Cyclophosphamide (N,%) 5(12,5) IgIV (N,%) 9 (22,5) Mycophenolate mofetil (N,%) 2(5) Rituximab (N,%) 6(15)Relapse N(%)23(57,5)Severe relapse (N,%)14(60,8)Non responder to corticosteroids/IgIV (N,%)1(2,5)Disclosure of InterestsNone declared
BackgroundLung involvement is the most common extra-articular manifestation. Rheumatoid arthritis related interstitial lung disease (RA-ILD) comprises a heterogeneous group of parenchymal lung disorders classified by distinct clinical, pathologic, and radiographic features. According to the current paradigm, circulating immune complexes and aberrant neutrophil extracellular trap formation (NETosis) contribute to disease pathogenesis.ObjectivesTo characterize the pattern of lung disease in “Attikon” RA-ILD cohort and develop insights about the pathophysiologic mechanisms via whole blood RNA sequencing.MethodsRetrospective and prospective study to identify clinical, laboratory and radiologic characteristics of patients with RA and pulmonary manifestations in the “Attikon” RA-ILD cohort. Changes in pulmonary function tests (PFTs), pattern of lung involvement (chest HRCT), disease activity (DAS28-ESR) and incidence of complications and comorbidities, were prospectively analyzed during the one-year follow-up period. Peripheral blood was collected in a subset of RA-ILD (n=11) and control RA patients (n=9) for RNA isolation and RNA sequencing. The gene expression profile of RA-ILD was inferred through differential gene expression analysis, followed by pathway and enrichment analyses.Results114 patients with RA-ILD were included [67% female, mean (SD) age at diagnosis 71.5 (9) years, 58% seropositive]. Non-specific interstitial pneumonia (NSIP) was the radiologic pattern most frequently observed (52%), followed by usual interstitial pneumonia (UIP) (24%). RA was diagnosed after ILD in 40% of patients. Mean (SD) FVC and DLCOsb at baseline was 80.5 (19.2) and 55.4 (19.5), respectively. Disease activity was lower in seropositive compared to seronegative both at baseline and at 1-year follow-up (p=0.025). PFTs at 12 months from baseline had been stabilized. Respiratory infections were observed in 17.6% of patients during the first year of follow-up, more common in the NSIP vs UIP group (p=0.01), possibly due to the higher doses of glucocorticoids in NSIP patients. RNA-sequencing analysis revealed a distinct gene expression profile in RA-ILD, characterized by the activation of type I interferon response, neutrophil activation and degranulation, and CCR1 chemokine interactions.ConclusionNSIP is the most frequent pattern of ILD in this RA-ILD cohort, carrying a higher risk for respiratory infections probably related to higher doses of glucocorticoid used. Myeloid cells’ migration via CCR1 and the formation of pro-inflammatory and pro-fibrotic NETs by activated neutrophils may contribute to RA-ILD pathogenesis.References[1]Y Dai et al, Rheumatoid arthritis–associated interstitial lung disease: an overview of epidemiology, pathogenesis and management Clin Rheumatol. 2021 Apr;40(4):1211-1220[2]X Zulma Yunt et al, Lung Disease in Rheumatoid Arthritis Rheum Dis Clin North Am. 2015 May;41(2):225-36Table 1.Patients’ characteristics with RA-ILD in Attikon cohortPatients CharacteristicsN=114Mean age71.5±9Female: Male76/38Smoking (current/ex)23/43Arterial hypertension71Diabetes mellitus32Dyslipidemia52COPD/BA17Thyroid disease30Latent TB17Seropositive66Diagnosis RA before ILD34Diagnosis RA after ILD45NSIP59UIP27Mixed NSIP-UIP5Organizing Pneumonia (OP)17Nodules21Disclosure of InterestsNone declared
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