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ObjectiveIgG4-related disease (IgG4-RD) is a heterogeneous, multiorgan condition of unclear aetiology that can cause organ failure. Difficulty recognising IgG4-RD contributes to diagnostic delays. We sought to identify key IgG4-RD phenotypes.MethodsWe used two cross-sectional studies assembled by an international, multispecialty network of IgG4-RD specialists who submitted 765 cases to derive and replicate phenotypic groups. Phenotype groups of disease manifestations and key covariate distributions across the identified groups were measured using latent class analysis.ResultsIn the derivation cohort (n=493), we identified four groups with distinct manifestations: Group 1 (31%), Pancreato-Hepato-Biliary disease; Group 2 (24%), Retroperitoneal Fibrosis and/or Aortitis; Group 3 (24%), Head and Neck-Limited disease and Group 4 (22%), classic Mikulicz syndrome with systemic involvement. We replicated the identification of four phenotype groups in the replication cohort. Compared with cases in Groups 1, 2 and 4, respectively, cases in Group 3 were more likely to be female (OR 11.60 (95% CI 5.39 to 24.98), 10.35 (95% CI 4.63 to 23.15) and 9.24 (95% CI 3.53 to 24.20)) and Asian (OR 6.68 (95% CI 2.82 to 15.79), 7.43 (95% CI 2.97 to 18.56) and 6.27 (95% CI 2.27 to 17.29)). Cases in Group 4 had a higher median serum IgG4 concentration (1170 mg/dL) compared with groups 1–3 (316, 178 and 445 mg/dL, respectively, pConclusionWe identified four distinctive IgG4-RD phenotypes according to organ involvement. Being Asian or female may predispose individuals to head and neck-limited disease. These phenotypes serve as a framework for identifying IgG4-RD and studying its aetiology and optimal treatment.

Background:Pulmonary Arterial Hypertension (PAH) is a rare but potentially fatal complication of Adult-Onset Still’s Disease (AOSD) (1). To date, only isolated observations have been published.Objectives:To establish the largest case series of AOSD patients with PAH, and to describe their clinical profile, evolution and response to treatments.Methods:Cases were retrospectively identified from the French PAH network database and from an online call of the “Club Rhumatismes et Inflammation” (http://www.cri-net.com). To be included, all patients had to fulfil the Yamaguchi or Fautrel’s criteria for AOSD and PAH had to be confirmed by right heart catheterization. The data were collected using a standardized questionnaire.Results:Thirteen patients were identified. All were female, the mean age at PAH diagnosis was 32± 12 years, 2 (15%) patients were Caucasian, 6 (46%) from Sub-Saharan Africa, 1 (8%) from Asia and 4 (31%) from West Indies. Only 2 (15%) patients were smokers. All patients had a systemic onset of AOSD, 12 had a polycyclic and 1 a chronic articular evolution, and the mean delay between AOSD and PAH diagnosis was 2.9 (range 1.7 -5.4) years. At PAH diagnosis, patients were receiving the following treatments: 13 (100%) corticosteroids (median dose 12 mg [interquartile range (IQR) 9-18]), 3 (23%) methotrexate, 8 (61%) interleukin (IL)-1 inhibitors (exposure median duration 6.7 months [IQR 3.6-8.5]), none IL-6 inhibitors, 2 (15%) TNF inhibitors. Six (46%) patients developed PAH during an AOSD flare. PAH was severe at diagnosis: 2 (15%), 7 (54%) and 4 (31%) patients were in NYHA functional class II, III and IV, respectively, with a median 6-minute walk distance of 289 m [IQR 0-448], a mean pulmonary arterial pressure of 41 ± 12 mmHg, a mean pulmonary arterial occlusion pressure of 6 ± 3 mmHg, a mean cardiac output of 3.9 ± 1.2 L/min, a mean cardiac index of 2.5 ± 0.9 L/min/m2 and a median pulmonary vascular resistance of 7 Wood Units [IQR 6-11]. The treatment prescribed after PAH diagnosis is detailed in the table. The median follow-up was 34 months [IQR 7-42]. Five patients (38.5 %) died. Figure 1 shows the overall survival. The haemodynamic response to PAH treatment seemed to be dissociated from the prognosis since several patients have died while their haemodynamic had improved or almost normalised.Conclusion:PAH is a rare but potentially severe complication of AOSD, leading to death in 38.5% of our cases series. AOSD remission should be physicians’ objective, since PAH seems to occur when the underlying disease is not controlled.References:[1]Feist E, Mitrovic S, Fautrel B. Mechanisms, biomarkers and targets for adult-onset Still’s disease. Nat Rev Rheumatol. 2018;1:603-618.Table 1.Therapeutic managementTreatmentn (%)Inotropic therapy5 (38%)HTAP treatment10 (77%)•0Monotherapy3•oInitial oral dual combination therapy3•nDual combination therapy including intravenous (IV) prostacyclin1•uUpfront triple combination therapy including IV prostacyclin3High-dose corticosteroids9 (69%)Interleukin 1 inhibitors initiation2 (15%)Interleukin 6 inhibitors initiation5 (38%)Acknowledgements:The authors want to thank the Club Rhumatismes et Inflammation for the diffusion of the online call.Disclosure of Interests:None declared

Background:Coronavirus disease 2019 (COVID-19) is a pandemic-spread systemic infectious disease with prominent respiratory manifestations and significant associated morbidity and mortality. Elderly people are most significantly affected with mortality ranging from 2.4% (age 60-69) to 19.6% (age>80) in European Countries. The prevalence of COVID-19 and of its complications in patients with immune-mediated disorders, remains unclear. The frequency and impact of COVID-19 on patients with IgG4-related diease (IgG4-RD), many of whom are on concurrent immunosuppression has not been addressed.Objectives:To assess the epidemiological and clinical relevance of COVID-19 in patients with IgG4-RD.Methods:This is a multi-centre retrospective observational study of IgG4-RD patients from France, Italy, Spain and the United Kingdom. Demographics, comorbidities, IgG4-RD features, current and past treatment along with COVID-19-suggestive symptoms and COVID-19 diagnoses from February 2020 to January 2021 were recorded by means of direct or phone interviews. Patients with reverse-transcriptase polymerase chain reaction-confirmed (cCOVID) or presumed COVID-19 based on clinical, serological or imaging features (pCOVID) were pooled for analysis (totCOVID) and compared to patients who were not diagnosed with COVID-19. Inter-group comparison of categorical and quantitative variables were performed by using the chi-square test with Fisher’s correction and the Mann-Whitney’s test respectively. Data are expressed as median (interquartile range) unless otherwise specified.Results:A total of 305 patients [71% males, median age 64 (54-74) years] were studied. Pancreato-biliary disease was the most frequently observed IgG4-RD phenotype (39%). Fifty-one percent of patients were taking corticosteroids at time of interview and 30% were on biological or conventional immunosuppressants. Thirty-two totCOVID cases (23 cCOVID, nine pCOVID) were identified: 11/32 were hospitalised, two needed intensive care and four (13%; 3/4 aged >80 years) died. Having one or more infected family members was a risk factor for COVID-19 in patients with IgG4-RD (OR=19.9; p20mg) or rituximab administration.Conclusion:The prevalence and course of COVID-19 in IgG4-RD patients are similar to those of the general population of the same age, with no evident impact of disease- or treatment-related factors to the basal infectious risk. Effective public health countermeasures might be beneficial for patients with IgG4RD.References:[1]European Centre for Disease Prevention and Control (ECDC): https://covid19-surveillance-report.ecdc.europa.eu/[2]Yang H, Ann Rheum Dis, 2021Disclosure of Interests:Giuseppe Alvise Ramirez: None declared, Marco Lanzillotta: None declared, Mikael Ebbo: None declared, Andreu Fernandez-Codina Consultant of: consulting fees from Atheneum Consulting, Gaia Mancuso: None declared, Fernando Martínez-Valle: None declared, Olimpia Orozco-Galvez: None declared, Nicolas Schleinitz: None declared, Lorenzo Dagna Consultant of: Abbvie, Amgen, Biogen, BristolMyers Squibb, Celltrion, Galapagos, GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI, Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unresctricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, GlaxoSmithKline,Janssen, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi Genzyme, and SOBI, Emma L. Culver: None declared, Emanuel Della Torre: None declared

Background:Women are at higher risk of thrombotic or severe bleeding complications during pregnancy, especially in the postpartum period (around 1%), but no prospective data have been available for women with antiphospholipid syndrome (APS). We report the first results of the French GR2 prospective study of pregnancy and rare diseases.Objectives:To describe the thrombotic and haemorrhagic events in APS patients included in the GR2 study and to identify risk factors associated with these complications.Methods:Women with APS and an ongoing pregnancy at 12 weeks of gestation were eligible for prospective inclusion in the GR2 study. Exclusion criteria were proteinuria (ratio > 1 g/g), serum creatinine > 100 µmol/L, or a multifetal pregnancy. Severe bleeding was defined as the need for transfusion, intensive care admission, or invasive treatment. Uteroplacental vascular insufficiency was defined as intrauterine growth restriction, preeclampsia, or HELLP syndrome.Results:The study included 119 pregnancies in 119 APS patients (53% thrombotic and 47% obstetric only APS). Treatment included aspirin (99%) and heparin (98%, in the therapeutic range for 50%).Twelve women (10%) had a thrombotic (n=5) and/or a severe haemorrhagic event (n=9).The thrombotic events included stroke (at 11 weeks; n=1), catastrophic APS (CAPS) (n=2), a pulmonary embolism (n=1), and portal vein thrombosis (n=1)(in the postpartum). Placental insufficiency was also present in 6 of these 12 women.Among the 22 (18.5%) women with at least one bleeding event (n=28), 9 (7.6%) had events defined as severe. Six of nine (67%) severe haemorrhages occurred in the postpartum and were directly related to the delivery. Two required an intrauterine balloon tamponade, two uterine arterial embolisation, and three surgery, including one hysterectomy.No women died.Finally, thrombotic and/or severe bleeding events during the postpartum period (n=9) were more frequent in women with lupus anticoagulant (14% versus 0%; P=0.01), with associated placental insufficiency (29% versus 3%; P=0.001) and with preterm delivery ≤34 weeks (33% versus 4%, P=0.002).Conclusion:Even though most women in our cohort received treatment based on current recommendations, a substantial number of maternal thrombotic and haemorrhagic events (10%) occurred. Despite several life-threatening complications, including CAPS, no women died.Most of the thrombotic or haemorrhagic events occurred in the peripartum period, and they were more frequent in women with the lupus anticoagulant, placental insufficiency, and preterm delivery.Although this morbidity rarely appears preventable, knowledge of the risk factors should increase awareness and help physicians to manage APS patients at particularly high risk.Disclosure of Interests:Anne Murarasu: None declared, Véronique LE GUERN Grant/research support from: UCB for GR2 study (to our institution), Gaêlle Guettrot Imbert: None declared, Elisabeth Pasquier: None declared, cecile yelnik: None declared, Viviane Queyrel: None declared, Nicolas Schleinitz: None declared, Nicole Ferreira-Maldent: None declared, Vincent Langlois: None declared, Geoffrey Urbanski: None declared, Catherine Deneux-Tharaux: None declared, Nathalie Costedoat-Chalumeau Grant/research support from: UCB to my institution

Background IgG4-related disease (IgG4-RD) is a recently recognized systemic condition characterized by unique pathological features that affect a wide variety of organs. Most available data come from descriptive series of patients with a unique organ involvement. Objectives To describe clinical and biological characteristics of IgG4-RD patients from a large multicentric national registry. Methods Cases were collected through a multicentric and multidisciplinary national registry between 2009 and 2014. Data were collected using a standardized form including clinical, biological, pathological and therapeutic findings. Results From 120 collected cases, 90 cases fulfilled comprehensive diagnostic criteria for IgG4-RD [1]. Patients presented with definite (44.5%), probable (24.4%) and possible (31.1%) IgG4-RD diagnosis. They were 64 males and 26 females ( sex ratio 2.5:1) with a median age at onset of 56 years. Ninety-three percent of patients presented with symptoms at diagnosis, including constitutional symptoms (45%), abdominal pain (26%), cough or dyspnea (17%) and sicca syndrome (15%). Median number of organs involved was 3 and 80% of patients had multi-organ involvement, defined by ≥3 organs involved. Lymph nodes (58.9%), pancreas (44.4%), kidney (32.2%), salivary glands (32.2%), retroperitoneum (28.9%) and biliary ducts (27.8%) were the most frequent tissues involved. Inflammatory pseudotumors (IPT) were observed in 30% of patients (pulmonary, orbital, hepatic, meningeal or breast IPT). IgG4 serum concentration was >135 mg/dl in 84% of patients, with a mean of 989 mg/dl (ranging from 30 to 5380). Polyclonal hypergammaglobulinemia was noted in 79% of cases, and low complement in 34%. Elevated C reactive protein level was observed in 48% of patients. Mean follow-up was 17.6 months (ranging from 0 to 94). Only ten patients (11%) did not require systemic therapy. Seventy-seven patients (86%) received steroids in first line therapy. A second line therapy was required in 36 patients (40%), with 20 patients treated with 3 lines of treatment or more. Indications of second line treatments were essentially represented by relapse or corticodependance. Second line treatments were azathioprine in 14 patients, rituximab in 10, mycophenolate mofetil in 3, cyclophosphamide in 3 and methotrexate in 2. Six patients underwent surgery, essentially for histological diagnosis because cancer was suspected. Conclusions As described in Asiatic populations, most IgG4-RD patients from our national registry present with multiple organ involvement. Localized disease is less frequent. Normal IgG4 levels are observed in 16% of patients. Steroids are usually effective, but almost half of patients require second line immunosuppressive therapy as steroid sparing agent or for relapse. References Umehara H, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012 Feb;22(1):21-30. Disclosure of Interest None declared

Background A pivotal role for Type I interferon (IFN) in SLE is supported by gene expression studies that identified the so-called type I IFN signature (IS). Objectives The aim of this study was to improve characterization of the blood-IFN signature in adult SLE patients. Methods Consecutive SLE patients fulfilling the ACR criteria were enrolled and followed-up prospectively. Microarray data were generated using Illumina beadchips. A modular transcriptional repertoire was employed as a framework for the analysis. Results Our repertoire of 260 modules, which consist of co-clustered gene sets, included 3 IFN-annotated modules (M1.2, M3.4 and M5.12) that were strongly up-regulated in SLE patients. At the individual level, a modular IS (ie, over-expression of at least 1 of the 3 IFN modules) was observed in 54/62 (87%) of patients or 131/157 (83%) of samples. The IFN signature was more complex than expected with each module displaying a distinct activation threshold (M1.2 Conclusions Modular repertoire analysis reveals complex IFN signatures in SLE, not restricted to the previous IFN-a signature, but involving also b and g IFNs. These modular IFN signatures may help in the design of disease activity biomarkers. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2405