POS0724 GENDER DIFFERENCES IN THROMBOTIC PRIMARY ANTIPHOSPHOLIPID SYNDROME IN A LARGE COHORT OF PATIENTS FROM FOUR EUROPEAN CENTERS

Background:Autoimmune diseases occur more frequently in females and their course and severity can be affected by gender. Antiphospholipid syndrome (APS) is a systemic autoimmune disorder in which antiphospholipid antibodies (aPL) exert a pathogenic role resulting in vascular thrombosis and/or pregnancy morbidities. Data about gender differences in thrombotic APS (t-APS) are still scarce1,2.Objectives:To evaluate the differences in frequency, disease expression and severity between females and males affected by primary t-APS.Methods:Retrospective study enrolling subjects with a formal diagnosis of primary APS (Miyakis 2006) with vascular thrombosis at onset. Women who presented with obstetric events as first aPL-related manifestation were excluded. All the patients were followed from 1967 to 2019 in four European centers: three French centers and one Italian center.Results:The study included 433 patients (68% females, 32% males). Median age at t-APS onset [31 (24-46) vs 41 (29-53) years, p<0.001] and at diagnosis [34 (27-50) vs 46 (34-57) years, p<0.001] was significantly lower in females.The most common presenting manifestations were venous thrombosis (60%) followed by arterial events (37%) and catastrophic APS (3%). Venous events were more frequent in women as compared to men (64% vs 51% p:0.012 OR:1.7 [1.1-2.5]). Sites of venous thrombosis included: limbs (35%), pulmonary (17%), cerebral (3%), portal and inferior cava (2%) and retinal (1%) veins, without gender differences. The arterial events were more frequent among men (43% vs 34% p:0.053). Strokes (27%) and myocardial infarctions (4%) were the most frequent manifestations, followed by thrombosis of limbs (2%), retina (2%) and abdominal organs (1%). Noteworthy, only men presented with visceral ischemia.During the follow-up, new thrombosis occurred in 41% of patients (179/433). 33% out of them had at least two episodes and these occurred especially among males (22% vs 10% p:0.001 OR:2.5 [1.3-4.8]). New events were mostly of the same type, but ⅓ of patients presented a switch from venous to arterial side and viceversa, with no gender differences.Complete aPL profile was available in 357 subjects: 33% had single aPL positivity, 24% double positivity and 43% triple positivity, with no differences between women and men. About 80% of the patients had a concomitant risk factor (RF) for thrombosis. Established cardiovascular RFs were more represented among men as shown in table 1. In women, estrogenic exposure was the main RFs, present in almost 40% of them.Table 1.MALESn= 137FEMALESn= 296POR [IC 95%]Traditional cardiovascular RFs, n (%)Smoke66 (48)81 (27)<0.0012.5 [1.6-3.8]Arterial hypertension59 (43)75 (25)<0.0012.2 [1.5-3.4]Dyslipidemia52 (38)72 (24)0.0041.9 [1.2-2.9]Diabetes16 (12)15 (5)0.0142.5 [1.8-5.1]Obesity13 (10)38 (13)nsOther thrombophilic factors, n (%)Estrogenic stimuli*0116 (39)-Trauma / surgery / immobilization21 (15)32 (11)nsCongenital thrombophilia9/94 (10)33/204 (16)nsData were compared using contingency tables, p value was calculated with Chi-Squared or Fisher exact test. *= hormonal therapy, pregnancy, post-partumConclusion:This gender-oriented analysis of patients with primary t-APS showed that women had the first vascular event at a younger age and mostly on the venous side, while men presented mainly with arterial events, later in life and suffered from more recurrent events. No differences were observed in the distribution of the aPL profile. The different frequency of arterial and venous events in the two groups could be attributed mainly to the presence of additional RFs rather than to biological gender-specific issues. However, it should be underlined that some RFs, such as the use of estrogens or classic cardiovascular RFs, are exclusive or more represented in one gender rather than the other, making it difficult to assess the link of causality between gender and manifestations of t-APS.References:[1]JF de Carvalho. Rheumatol Int. 2011.[2]LJ Jara. Lupus. 2005.Disclosure of Interests:None declare

THU0275 SEVERE PREECLAMPSIA RELATED TO ANTIPHOSPHOLIPID SYNDROME: AN EUROPEAN STUDY OF 40 WOMEN

Background:One of the 3 features of obstetrical antiphospholipid syndrome (APS) is severe preeclampsia (PE). Its time of occurrence, the associated risk of thromboses and systemic lupus erythematosus (SLE) have not been reported yet.Objectives:We analyzed severe PE in a series of women with APS.Methods:We retrospectively collected data of female patients from 5 French internal medicine and 1 Italian rheumatology units. Inclusion criteria were: a severe PE/eclampsia(1), that occurred before 34 weeks of gestation (WG) in patients who met the APS classification criteria(2).Results:40 patients were enrolled (Table 1). Because of known APS/positive aPL/previous obstetrical complications, 23(57.5%) patients were treated during the index PE: 4 with low dose aspirin (LDA), 4 with low molecular weight heparin (LMWH), and 15 with a combination of both. 7 patients were also treated with hydroxychloroquine, 8 with corticosteroids and 3 with immunosuppressants. 17(42.5%) patients received no treatment. 24(60%) live births were observed. During a follow-up period of 3 years, 26(65%) patients had at least 1 new pregnancy, with a total of 38 pregnancies which resulted in 33(86.8%) live births. 57.5% pregnancies who resulted in live births occurred without any maternal or fetal complications. All 26 patients who had at least 1 pregnancy after index PE were treated with LDA; LMWH was given at prophylactic and therapeutic dosage in 13(50%) patients, respectively. No patient experienced 3 consecutive miscarriages.Table 1.40 APS patients with severe PEOverall features (n, %)Patients40 (100)Age at PE, (median, IQR)30.5 (27-33)PE term, WG (median, IQR)25.5 (23-29) Live births24 (60) Birth term, WG (median, IQR)25.5 (23.7-30.3) Associated SLE12 (30)Maternal complications (n, %)25 (62.5) HELLP18 (45) E6 (15) CAPS3 (7.5) Placental abruptions3 (7.5)Fetal complications (n, %)31 (77.5) IUGR18 (45) IUFD11 (2.5) Preterm delivery22 (55)Obstetrical history (n, %) Primiparous21 (52.5) Index PE before APS12 (30)Thrombosis (n, %) Thrombosis before PE index14 (35.0) Thrombosis after PE index2 (5.0)Abs at APS diagnosis (n, %) aPL triple positivity21 (52.5) IgG/IgM anti-cardiolipin34 (85.0) IgG/IgM anti-β2GPI25 (62.5) LAC33 (82.5)Legend to Table 1:PE: preeclampsia; APS: antiphospholipid syndrome; IQR: interquartile range; WG: weeks of gestation; SLE: systemic lupus erythematosus; HELLP: Hemolysis, elevated liver enzymes, low platelet; E: eclampsia; CAPS: catastrophic APS; IUGR: intrauterine growth restriction; IUFD: intrauterine fetal death; CHB: congenital atrioventricular block; aPL: antiphospholipid antibodies; LAC: lupus anticoagulant.Conclusion:Among the APS criteria, "3 consecutive miscarriages criterion" was not found. The majority of patients also experienced thrombosis and SLE before the index PE.References:[1]Diagnosis and Management of preeclampsia and eclampsia. International Journal of Gynecology &Obestetrics 2002;77:67-75.[2]Miyakis S, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295e 306.Disclosure of Interests:Maddalena Larosa: None declared, Nathalie Morel: None declared, Meriem BELHOCINE: None declared, Amelia Ruffatti: None declared, Nicolas Martin Silva: None declared, Romain Paul: None declared, Luc Mouthon: None declared, Michel DREYFUS: None declared, Jean-Charles PIETTE: None declared, Odile Souchaud-Debouverie: None declared, Catherine Deneux-Tharaux: None declared, Vassilis Tsatsaris: None declared, Emmanuelle Pannier: None declared, Gaêlle Guettrot Imbert: None declared, Véronique LE GUERN Grant/research support from: UCB for GR2 study (to our institution), Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS, Nathalie Costedoat-Chalumeau Grant/research support from: UCB to my institutio

Relapsing polychondritis: state of the art on clinical practice guidelines

Due to the rarity of relapsing polychondritis (RP), many unmet needs remain in the management of RP. Here, we present a systematic review of clinical practice guidelines (CPGs) published for RP, as well as a list of the most striking unmet needs for this rare disease. We carried out a systematic search in PubMed and Embase based on controlled terms (medical subject headings and Emtree) and keywords of the disease and publication type (CPGs). The systematic literature review identified 20 citations, among which no CPGs could be identified. We identified 11 main areas with unmet needs in the field of RP: the diagnosis strategy for RP; the therapeutic management of RP; the management of pregnancy in RP; the management of the disease in specific age groups (for instance in paediatric-onset RP); the evaluation of adherence to treatment; the follow-up of patients with RP, including the frequency of screening for the potential complications and the optimal imaging tools for each involved region; perioperative and anaesthetic management (due to tracheal involvement); risk of neoplasms in RP, including haematological malignancies; the prevention and management of infections; tools for assessment of disease activity and damage; and patient-reported outcomes and quality of life indicators. Patients and physicians should work together within the frame of the ReCONNET network to derive valuable evidence for obtaining literature-informed CPGs

Renal transplantation for lupus nephritis: non-adherence and graft survival

Objectives: Poor adherence to immunosuppressive treatment is common in patients with systemic lupus erythematosus and may identify those with lupus nephritis (LN) who have a poorer prognosis. Non-adherence has also been reported to be a potential adverse outcome predictor in renal transplantation (rTp). We investigated whether non-adherence is associated with increased rTp graft rejection and/or failure in patients with LN. Methods: Patients with LN undergoing rTp in two major London hospitals were retrospectively included. Medical and electronic records were reviewed for documented concerns of non-adherence as well as laboratory biochemical drug levels. The role of non-adherence and other potential predictors of graft rejection/failure including demographics, comorbidities, age at systemic lupus erythematosus and LN diagnosis, type of LN, time on dialysis prior to rTp and medication use were investigated using logistic regression. Results: Out of 361 patients with LN, 40 had rTp. During a median follow-up of 8.7 years, 17/40 (42.5%) of these patients had evidence of non-adherence. A total of 12 (30.0%) patients experienced graft rejection or failure or both. In the adherent group 2/23 (8.7%) had graft rejection, whilst in the non-adherent this rose to 5/17 (29.4%, p = 0.11). Graft failure was seen in 5/23 (21.7%) patients from the adherent group and 4/17 (23.5%) in the non-adherent group (p = 0.89). Non-adherent patients had a trend towards increased graft rejection, hazard ratio 4.38, 95% confidence interval = 0.73–26.12, p = 0.11. Patients who spent more time on dialysis prior to rTp were more likely to be adherent to medication, p = 0.01. Conclusion: Poor adherence to immunosuppressive therapy is common and has been shown to associate with a trend towards increased graft failure in patients with LN requiring rTp. This is the first paper to report that shorter periods on dialysis prior to transplantation might lead to increased non-adherence in lupus patients

Arthritis in primary Sjögren&#039;s syndrome: Characteristics, outcome and treatment from French multicenter retrospective study

Objective To describe the characteristics and the outcome of primary Sjögren Syndrome (pSS) associated arthritis and to compare the efficacy of different therapeutic regimen. Methods We conducted a retrospective study using Club Rhumatisme and Inflammation (CRI) and French Internal Medicine Society (SNFMI) networks. All patients with a diagnosis of pSS and at least one episode of clinical and/or echographic synovitis were included. Patients with synovitis (cases) were compared to pSS patients without synovitis (controls). Results 57 patients (93% women) were included with a median age of 54 years [45–63]. Patients with synovitis had more frequently lymph node enlargement (12.3% vs. 1.8%, p = .007) and a higher ESSDAI score (8 [6–12] vs. 2 [1–4], p &lt; .0001). There was no difference concerning CRP levels, rheumatoid factor and cyclic citrullinated peptide (CCP)-antibodies positivity. Among 57 patients with synovitis, 101 various treatment courses have been used during the follow-up of 40 [22.5–77] months. First treatment course consisted in steroids alone (3.5%), steroids in association (79%) with hydroxychloroquine (HCQ) (49%), methotrexate (MTX) (35%), rituximab (RTX) (5.3%) or other immunosuppressive drugs (7%). HCQ, MTX, and RTX were associated with a significant reduction of tender and swollen joint count, and a significant steroids-sparing effect. No difference could be shown for the joint response between these treatment regimens. Conclusion pSS articular manifestations may include synovitis which could mimic rheumatoid arthritis but differ by the absence of structural damage. Even if the use of HCQ, MTX, and RTX seem to be effective for joint involvement, the best regimen remains to be determined

Stewart-Treves syndrome: MR imaging of a postmastectomy upper-limb chronic lymphedema with angiosarcoma

The rare occurrence of angiosarcoma in postmastectomy upper-limb lymphedema with magnetic resonance (MR) imaging is discussed. Unfamiliarity with this aggressive vascular tumor and its harmless appearance often leads to delayed diagnosis. Angiosarcoma complicating chronic lymphedema may be low in signal intensity on T2-weighting and short tau inversion recovery (STIR) imaging reflecting the densely cellular, fibrous stroma, and sparsely vascularized tumor histology. Additional administration of intravenous contrast medium revealed significant enhancement of the tumorous lesions. Awareness of angiosarcoma and its MR imaging appearance in patients with chronic lymphedema may be a key to early diagnosis or allow at least inclusion in the differential diagnosis

Treat-to-target in systemic lupus erythematosus: recommendations from an international task force.

The principle of treating-to-target has been successfully applied to many diseases outside rheumatology and more recently to rheumatoid arthritis. Identifying appropriate therapeutic targets and pursuing these systematically has led to improved care for patients with these diseases and useful guidance for healthcare providers and administrators. Thus, an initiative to evaluate possible therapeutic targets and develop treat-to-target guidance was believed to be highly appropriate in the management of systemic lupus erythematosus (SLE) patients as well. Specialists in rheumatology, nephrology, dermatology, internal medicine and clinical immunology, and a patient representative, contributed to this initiative. The majority convened on three occasions in 2012-2013. Twelve topics of critical importance were identified and a systematic literature review was performed. The results were condensed and reformulated as recommendations, discussed, modified and voted upon. The finalised bullet points were analysed for degree of agreement among the task force. The Oxford Centre level of evidence (LoE, corresponding to the research questions) and grade of recommendation (GoR) were determined for each recommendation. The 12 systematic literature searches and their summaries led to 11 recommendations. Prominent features of these recommendations are targeting remission, preventing damage and improving quality of life. LoE and GoR of the recommendations were variable but agreement was >0.9 in each case. An extensive research agenda was identified, and four overarching principles were also agreed upon. Treat-to-target-in-SLE (T2T/SLE) recommendations were developed by a large task force of multispecialty experts and a patient representative. It is anticipated that 'treating-to-target' can and will be applicable to the care of patients with SLE