Hydroxychloroquine levels in pregnancy and materno-fetal outcomes in Systemic Lupus Erythematosus patients.

OBJECTIVES: Data about hydroxychloroquine (HCQ) levels during pregnancy are sparse. We assessed HCQ whole blood levels at first trimester of pregnancy as a potential predictor of maternal and obstetric/fetal outcomes in patients with systemic lupus erythematosus (SLE). METHODS: We included pregnant SLE patients enrolled in the prospective GR2 study receiving HCQ, with at least one available first-trimester whole-blood HCQ assay. We evaluated several cut-offs for HCQ whole blood levels, including ≤200 ng/ml for severe non-adherence. Primary outcomes were maternal flares during the second and third trimesters of pregnancy, and adverse pregnancy outcomes (APOs: fetal/neonatal death, placental insufficiency with preterm delivery, and small-for-gestational-age neonates). RESULTS: We included 174 patients (median age: 32.1 years, IQR 28.8-35.2). Thirty (17.2%) patients had flares, 4 (2.3%) being severe. APOs occurred in 28 patients (16.1%). There were no significant differences in APOs by HCQ level for either those with subtherapeutic HCQ levels (≤500 ng/ml vs >500 ng/ml: 23.5% vs 14.3%, p = 0.19) or those with non-adherent HCQ levels (≤200 ng/ml vs >200 ng/ml: 20.0% vs 15.7%, p = 0.71). Similarly, the overall rate of maternal flares did not differ significantly by HCQ level cut-off, but patients with subtherapeutic (HCQ ≤500 ng/ml: 8.8% vs 0.7%, p = 0.02) and non-adherent HCQ levels (≤200 ng/ml: 13.3% vs 1.3%, p = 0.04) had significantly more severe flares. CONCLUSION: In this large prospective study of pregnant SLE patients, first-trimester subtherapeutic (≤500 ng/ml) and severe non-adherent (≤200 ng/ml) HCQ levels were associated with severe maternal flares, but not with APOs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02450396.

Prognostic value of 18 FDG-PET at diagnosis and follow-up in giant cell arteritis: An observational restrospective study.

OBJECTIVES: To evaluate the ability of 18FDG PET/CT, at diagnosis of giant cell arteritis (GCA) and during follow-up, to predict occurrence of relapse in large-vessel GCA (LV-GCA). METHODS: We conducted a retrospective study using the French Study Group for Large-Vessel Vasculitis (GEFA) network. Data from patients with LV-GCA diagnosed by PET/CT and who had PET/CT in the following year were collected. For each PET/CT, PET vascular activity score (PETVAS) and total vascular score (TVS) were assessed, and their ability to predict the occurrence of subsequent relapse was assessed. RESULTS: A total of 65 LV-GCA patients were included, of whom 55 had undergone a follow-up PET/CT 3 to 12 months after the diagnosis of GCA. Patients for whom the second PET/CT (PET2) was performed during active GCA were excluded. PETVAS and TVS decreased between PET1 and PET2 in all patients (p < 0.001). There was no correlation between vascular activity scores in PET2 and time to prednisone taper. For relapse prediction, at PET1, the AUC of the TVS and PETVAS were respectively 51.9 and 41.9 at 6 months, 55.3 and 49.7 at 1 year, 55 and 55.7 at 2 years. For PET2, the AUC were respectively 46.1 and 46.7 at 6 months, 52.1 and 48.9 at 1 year, 58.4 and 52.3 at 2 years. CONCLUSION: PET vascular activity scores at diagnosis and at follow-up PET/CT performed outside a period of GCA activity do not display high performance to predict the occurrence of subsequent relapse in LV-GCA patients.

Inaugural dropped head syndrome and camptocormia in inflammatory myopathies: a retrospective study.

OBJECTIVES: Inaugural axial muscle involvement, defined as dropped head syndrome (DHS) and/or camptocormia (CC), is poorly described in inflammatory myopathies (IM). This study aimed to further characterize IM patients with inaugural DHS/CC, their outcome and care management. METHODS: This retrospective study included IM patients diagnosed between 2000 and 2021. The main inclusion criterion was IM revealed by axial muscle deficit (DHS/CC). RESULTS: Twenty-seven patients were included; median (IQR) age at first symptoms was 66.0 years (55.5-75.0); 21 were female (77.8%). There were nine IBM, 33.3%, nine overlap myositis (OM, 33.3%), five DM, 18.5%, two immune checkpoint inhibitor-related myositis (7.4%), one focal myositis (3.7%) and one myositis with anti-Hu antibodies (3.7%). Age at first symptoms was ≤70 years in 16 patients (59.3%), including all DM patients and 8/9 OM patients (88.9%). In this group, partial remission of the disease was obtained in 9/16 (56.3%) and complete remission in 1/16 patients (6.3%); regression of DHS/CC was achieved in 3/16 patients (18.8%). Conversely, in the group of 11 patients aged >70 years at first symptoms, there were eight IBM (72.7%). Partial remission was obtained in 5/11 patients (45.5%), the disease was stable in 6/11 patients (54.5%); no complete remission was obtained nor regression of DHS/CC. CONCLUSION: The analysis of IM patients with inaugural DHS/CC delineates two groups of patients according to the age at first symptoms in terms of clinical and outcome specificities, and proposes an adapted diagnostic and care management approach to prevent long-term complications.

Clinical features and long-term outcomes of patients with systemic polyarteritis nodosa diagnosed since 2005: Data from 196 patients.

BACKGROUND: The landscape of polyarteritis nodosa (PAN) has substantially changed during the last decades. Recent data regarding causes, characteristics, and prognosis of systemic PAN in the modern era are lacking. METHODS: This retrospective study included patients with systemic PAN referred to the French Vasculitis Study Group between 2005 and 2019. Characteristics, associated conditions and outcomes were collected, and predictors of relapse and death were analyzed. RESULTS: 196 patients were included. Main clinical symptoms were constitutional (84%), neurological (59%), skin (58%) and musculoskeletal (58%) manifestations. Secondary PAN accounted for 55 (28%) patients, including myelodysplastic syndrome (9%), solid cancer (7%), lymphoma (4%) and autoinflammatory diseases (4%). No patient had active HBV infection. All treated patients (98.5%) received glucocorticoids (GCs), alone (41%) or in combination with immunosuppressants (59%), with remission achieved in 90%. Relapses were independently associated with age >65 years (HR 1.85; 95% CI1.12-3.08), gastrointestinal involvement (1.95; 95% CI1.09-3.52) and skin necrotic lesions (HR 1.95; 95%CI 1.24-3.05). One-, 5- and 10-year overall survival rates were 93%, 87% and 81%, respectively. In multivariate analyses, age >65 years (HR 2.80; 95%CI 1.23-6.37), necrotic purpura (HR 4.16; 95%CI 1.62-10.70), acute kidney injury (HR 4.89; 95% 1.71-13.99) and secondary PAN (HR 2.98; 95%CI 1.29-6.85) were independently associated with mortality. CONCLUSION: Landscape of PAN has changed during the last decades, with the disappearance of HBV-PAN and the emergence of secondary PAN. Relapse rate remains high, especially in aged patients with gastrointestinal and cutaneous necrosis, as well as mortality.

Occurrence of focal myositis during Behçet's disease: The identification of a specific vasculitis-associated focal myopathy.

AIMS: This study aimed to report the association of focal myositis (FM) and Behçet's disease (BD) and to analyse the main characteristics of such an association. METHODS: This is a retrospective multicentre study of patients with BD and FM (BD + FM+ group) and those without FM (BD - FM+ group). Clinical, laboratory, radiological, pathological, treatment and outcome data were analysed. RESULTS: The BD + FM+ group included 10 patients; the median [interquartile range] age at BD diagnosis was 25 [16-35] years, and at FM diagnosis, it was 30 [26-42] years. The diagnosis of BD preceded FM in the majority of cases (n = 8/10). FM occurrence was associated with BD flare-ups in three cases. The creatine kinase levels remained normal or slightly increased. Histological analyses identified relatively preserved muscle tissue, associated with vasculitis (n = 5/6). All patients required treatment; most patients relapsed (n = 9/10). The BD - FM+ group included 35 patients. A comparison of the groups identified a trend towards a younger median age at diagnosis of FM among those with BD (p = 0.063) and more frequent focal muscle swelling in the BD + FM+ group (p = 0.029). The pathological analysis identified significantly less frequent muscle alterations in the BD + FM+ group (muscle fibre size heterogeneity, p = 0.021; necrosis, p = 0.007; and fibrosis, p = 0.027). BD + FM+ patients had a higher frequency of relapse (p = 0.003) and systematic treatment (p = 0.042). CONCLUSIONS: FM occurring during BD appears to be part of the systemic vasculitis process and presents as a vasculitis-associated focal myopathy with a specific clinico-histological pattern. Patients with this association require long-term follow-up and adapted management. This case series also highlights the need for research on BD diagnostic criteria in cases of FM.

Disease patterns and specific trajectories of anti-MDA5-related disease: a multicentre retrospective study of 70 adult patients.

Introduction: This study aimed to provide an updated analysis of the different prognostic trajectories of patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibodies. Methods: Among a cohort of 70 patients, baseline characteristics and phenotypes, treatments and outcomes were analyzed. A Cox proportional hazards model was used to identify factors associated with poor outcomes, i.e., death or progressive disease at the last follow-up. Results: Among the 70 patients, 45 were women, and 54 were Caucasian. A dermatologic involvement was observed in 58 (83%) patients, including 40 with MDA5 vasculopathy-related skin lesions. Muscular involvement was observed in 39 (56%) patients. Interstitial lung disease (ILD) was observed at baseline in 52 (74%) patients, including 23 (44%) who developed rapidly progressive (RP) ILD. Seven (10%) patients showed thromboembolic complications within the first weeks of diagnosis, and eight (11%) other patients developed a malignancy (4 before the diagnosis of anti-MDA5 disease). Poor outcomes were observed in 28 (40%) patients, including 13 (19%) deaths. Among the 23 patients with RP-ILD, 19 (79%) showed poor outcomes, including 12 (63%) who died. In multivariate analyses, RP-ILD (hazard ratio (HR), 95% CI: 8.24 [3.21-22], p<0.0001), the occurrence of thromboembolic events (HR: 5.22 [1.61-14.77], p=0.008) and the presence of any malignancy (HR: 19.73 [6.67-60], p<0.0001) were the three factors independently associated with poor outcomes. Discussion: This new independent cohort confirms the presence of different clinical phenotypes of anti-MDA5 diseases at baseline and the poor prognosis associated with RP-ILD. Thromboembolic events and malignancies were also identified as prognostic factors.

Pregnancy outcomes in women with primary Sjögren's syndrome: an analysis of data from the multicentre, prospective, GR2 study.

BACKGROUND: Adverse pregnancy outcomes in women with primary Sjögren's syndrome have only been evaluated retrospectively using heterogeneous methods and with contradictory results. We aimed to describe adverse pregnancy, delivery, and birth outcome risks in pregnant women with primary Sjögren's syndrome compared with those of a matched general population in France, and to identify factors predictive of disease flares or adverse pregnancy outcomes. METHODS: We conducted a multicentre, prospective, cohort study in France using the GR2 (Groupe de Recherche sur la Grossesse et les Maladies Rares) registry. Women from the GR2 study were eligible if they had conceived before March, 2021, had primary Sjögren's syndrome according to the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) 2016 classification criteria, and had an ongoing pregnancy at 12 weeks of gestation. In women who entered in the registry with pregnancies before 18 weeks of gestation, we sought to identify factors associated with primary Sjögren's syndrome flare (≥3-point increase in EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI] score) or adverse pregnancy outcomes (fetal or neonatal death, placental insufficiency leading to a preterm delivery [<37 weeks of gestation], or small-for-gestational-age birthweight). A matched controlled study compared adverse pregnancy, delivery, and birth outcome rates between pregnant women with primary Sjögren's syndrome from the GR2 registry and matched controls from the general population included in the last French perinatal survey (Enquête Nationale Périnatale 2016). FINDINGS: 1944 pregnancies were identified in the GR2 cohort, of which 106 pregnancies in 96 women with primary Sjögren's syndrome were included in this analysis. The median age at pregnancy onset was 33 years (IQR 31-36). 87 (83%) of 105 pregnancies (with ethnicity data) were in White women, 18 (17%) were in Black women; 92 (90%) of 102 had previous systemic activity (ESSDAI score of ≥1; data missing in four pregnancies), and 48 (45%) of 106 had systemic activity at inclusion. Of 93 pregnancies included at week 18 of gestation or earlier, primary Sjögren's syndrome flares occurred in 12 (13%). No baseline parameters were associated with primary Sjögren's syndrome flare. Four twin pregnancies and one medical termination were excluded from the adverse pregnancy outcome analysis; of the remaining 88, adverse pregnancy outcomes occurred in six (7%). Among pregnancies in women with data for antiphospholipid antibodies (n=55), antiphospholipid antibody positivity was more frequent among pregnancies with adverse outcomes (two [50%] of four pregnancies) compared with those without adverse outcomes (two [4%] of 51 pregnancies; p=0·023). Anti-RNP antibody positivity was also more frequent among pregnancies with adverse outcomes than those without, although this was not statistically significant. In the matched controlled study, adverse pregnancy outcomes occurred in nine (9%) of 105 pregnancies in women with primary Sjögren's syndrome and 28 (7%) of the 420 matched control pregnancies; adverse pregnancy outcomes were not significantly associated with primary Sjögren's syndrome (odds ratio 1·31, 95% CI 0·53-2·98; p=0·52). INTERPRETATION: Pregnancies in women with primary Sjögren's syndrome had very good prognoses for mothers and fetuses, with no overall increase in adverse pregnancy outcome risk compared with the general population. Women with antiphospholipid antibodies or anti-RNP antibodies require close monitoring, because these factors might be associated with a higher risk of adverse pregnancy outcomes. FUNDING: Lupus France, Association des Sclérodermiques de France, Association Gougerot Sjögren, Association Francophone Contre la Polychondrite Chronique Atrophiante, AFM-Telethon, Société Nationale Française de Médecine Interne, Société Française de Rhumatologie, Cochin Hospital, French Health Ministry, Fondation for Research in Rheumatology, Association Prix Véronique Roualet, Union Chimique Belge.

Infection Risk in Patients with Dermatomyositis Associated with Anti-MDA5 Antibodies: A Historical Cohort Study.

Objective: Dermatomyositis associated with anti-MDA5 autoantibodies (DM-MDA5+) is a rare autoimmune disease usually characterized by skin involvement, often-severe lung involvement, and general features. Several reports of infections have been described, sometimes early after the introduction of immunosuppressive therapy. We studied the infection risk in a DM-MDA5+ population. Methods: A retrospective cohort study comparing the number and type of infections during the follow-up of 19 patients with DM-MDA5+ and 37 patients with another type of inflammatory myopathy was analyzed. Patients in both groups were matched on initial immunosuppressive therapy. We described and compared significant infectious complications (SIC) in each group. Results: Patients DM-MDA5+ had more SIC: 27 events in the DM-MDA5+ group versus 6 in the controls (HR 7.08, 95% CI 2.50−20.04, p < 0.0001). The number of SIC per patient was higher in DM-MDA5+ (1.4 ± 1.57 vs. 0.16 ± 0.44, p < 0.001). These were mainly lung (n = 13, 48%) and skin infections (n = 6, 22%), more often infections of an undetermined infectious agent (n = 11, 41%) or of bacterial origin (n = 9, 33%). A few cases of opportunistic infections were reported. The median duration of follow-up without SIC event in the DM-MDA5+ cohort was 3.5 months. Conclusion: Patients with DM-MDA5+ have an increased infection risk compared to others inflammatory myopathies irrespective of immunosuppressive therapy exposure. These results highlight the importance of monitoring for infection during patient follow-up.

The Spectrum of Still's Disease: A Comparative Analysis of Phenotypic Forms in a Cohort of 238 Patients.

Still's disease (SD) is a heterogeneous autoinflammatory disorder for which several phenotypes have been described. We conducted a retrospective study to re-evaluate the dichotomous view of the disease, to compare the juvenile and adult forms, and to look for prognostic factors. We collected data from ten French centers, seeking patients with a diagnosis of adult-onset SD (AOSD) or systemic juvenile idiopathic arthritis (sJIA). We identified 238 patients, 152 (64%) of whom had AOSD while 86 (36%) had sJIA. The median age at SD onset was 26.6 years. In patients with identifiable patterns, the course of SD was systemic in 159 patients (74%), chronic in 55 (26%). Sore throat and myalgia were more frequent in patients with AOSD. Abnormal liver tests, serum ferritin and C-reactive protein levels were higher in AOSD group. Fever and skin rash were predictive of complete remission or recovery and high lactate dehydrogenase level was a poor prognosis factor. Symptoms such as splenomegaly, skin rash, high polymorphonuclear neutrophils count and macrophage activation syndrome were predictive of a systemic phenotype. Overall, there were no major differences between sJIA and AOSD. Our results are consistent with the "biphasic" model of an autoinflammatory disease that can progress to chronic arthritis if not treated early.

Immunoglobulin A Vasculitis Following COVID-19: A French Multicenter Case Series.

OBJECTIVE: Immunoglobulin A vasculitis (IgAV) usually occurs following viral respiratory tract infection. In the context of the global coronavirus disease 2019 (COVID-19) pandemic, we describe a case series of patients who developed IgAV following SARS-CoV-2 infection. METHODS: This national multicenter retrospective study included patients with IgAV following SARS-CoV-2 infection from January 1, 2020, to January 1, 2022. Patients had histologically proven IgAV and reverse transcription PCR (RT-PCR)-proven SARS-CoV-2 infection. The interval between infection and vasculitis onset had to be < 4 weeks. RESULTS: We included 5 patients, 4 of whom were women with a mean age of 45 years. Four patients had paucisymptomatic infections and 1 required a 48-hour low-flow oxygen treatment. All 5 patients had purpuric skin involvement. Arthritis was observed in 2 patients, 3 had IgA glomerulonephritis, and 2 had digestive involvement. Three renal biopsies were performed and showed mesangial IgA deposits without any extracapillary proliferation. Median C-reactive protein was 180 (range 15.1-225) mg/L, median serum creatinine level was 65 (range 41-169) µmol/L, and 2 patients had a glomerular filtration rate < 60 mL/min. Four patients received first-line treatment with glucocorticoids. All patients had a favorable progression and 2 patients experienced minor skin relapses, one after COVID-19 vaccination. CONCLUSION: This series describes the emergence of IgAV closely following COVID-19; we were not able to eliminate an incidental link between these events. Their disease outcomes were favorable. In most of our patients, the SARS-CoV-2 infection was paucisymptomatic, and we recommend RT-PCR tests to look for COVID-19 in patients without any evident triggers for IgAV.

Identification of Multidimensional Phenotypes Using Cluster Analysis in Sarcoid Uveitis Patients.

PURPOSE: To identify multidimensional phenotypes of sarcoid uveitis patients. DESIGN: Retrospective cohort. METHODS: Consecutive patients with biopsy-proven, presumed, or probable sarcoid uveitis between December 2003 and December 2020 in Lyon were recruited. Data were collected from the clinical notes, and consisted in laboratory and imaging findings, systemic treatments and outcome. Systemic sarcoidosis was diagnosed according to the Abad's modified criteria and uveitis was classified according to the Standardization of Uveitis Nomenclature. A hierarchical cluster analysis was performed. The main outcome measure was identification of different phenotypes of sarcoid uveitis patients. RESULTS: A total of 299 patients were included. Three clusters were identified: (1) younger non-Caucasian patients who presented acute (75.3%), anterior (55.6%) uveitis, and systemic manifestations (87.8%), requiring oral corticosteroids (75.3%) along with immunosuppressive therapy (17.2%) and who were more prone to experience complete visual recovery (84.1%); (2) middle-aged Caucasian patients who presented chronic (91.7%), panuveitis (79.5%), and isolated uveitis at diagnosis (74.8%), requiring systemic treatment with corticosteroids (74.0%) but less frequently immunosuppressive therapy (9.8%) and a worse prognosis (45.3% complete visual recovery); and (3) middle-aged Caucasian patients, without preferential chronic or acute uveitis, isolated uveitis at diagnosis (81.4%), more homogenous in terms of eye involvement repartition, requiring less corticosteroids or immunosuppressive therapy (respectively 54.1% and 13.1%) and having a prognosis close to cluster 2 patients (55.3% complete visual recovery). CONCLUSIONS: This retrospective study suggested the existence of several phenotypes of sarcoid uveitis patients with different progressions and prognoses. Further studies are needed to determine the genetic and environmental factors that could explain these results.

Clonal haematopoiesis of indeterminate potential and cardiovascular events in systemic lupus erythematosus (HEMATOPLUS study).

OBJECTIVE: The detection of somatic mutations among the genes of myeloid cells in asymptomatic patients-defining clonal haematopoiesis of indeterminate potential (CHIP)-is associated with a predisposition to cardiovascular events (CVEs) in the general population. We aimed to determine whether CHIP was associated with CVEs in SLE patients. METHODS: The study is an ancillary study of the randomized, double-blind, placebo-controlled, multicentre PLUS trial conducted from June 2007 through August 2010 at 37 centres in France, involving 573 SLE patients. The search for somatic mutations by high-throughput sequencing of 53 genes involved in clonal haematopoiesis was performed on genomic DNA collected at PLUS inclusion. CHIP prevalence was assessed in SLE and in a retrospective cohort of 479 patients free of haematological malignancy. The primary outcome was an incident CVE in SLE. RESULTS: Screening for CHIP was performed in 438 SLE patients [38 (29-47) years, 91.8% female]. Overall, 63 somatic mutations were identified in 47 patients, defining a CHIP prevalence of 10.7% in SLE. Most SLE patients (78.7%) carried a single mutation. Most variants (62.5%) were located in the DNMT3A gene. CHIP frequency was related to age and to age at SLE diagnosis, and was associated with a lower frequency of aPLs. CHIP occurred >20 years earlier (P < 0.00001) in SLE than in controls. The detection of CHIP at inclusion was not found to be associated with occurrence of CVEs during follow-up [HR = 0.42 (0.06-3.21), P = 0.406]. CONCLUSION: The prevalence of CHIP is relatively high in SLE for a given age, but was not found to be associated with incident CVEs. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT05146414.

Immune thrombocytopenia with clinical significance in systemic lupus erythematosus: a retrospective cohort study of 90 patients.

OBJECTIVES: To describe the characteristics, treatment and outcome of patients with immune thrombocytopenia with clinical significance (ITPCS) associated with SLE. METHODS: This retrospective multicentre study included SLE patients who experienced ≥1 ITPCS (defined as ITP with attributable bleeding disorders and/or a platelet count <30×109/l). Other causes of secondary thrombocytopenia were excluded. Major bleeding event (MBG) was defined as Khellaf score >8 and/or WHO score >2. RESULTS: A total of 90 patients were included, the median (range) follow-up duration was 80 (6-446) months. ITP was diagnosed before SLE in 25 patients. They presented a high rate of autoimmune haemolytic anaemia (15%), antiphospholipid antibody (62%) and antiphospholipid syndrome (19%). The 25 (28%) patients who experienced MBG had significantly more bleedings at ITP diagnosis and higher bleeding scores, and serositis and thrombosis during follow-up. They required significantly more treatment lines, transfusions and hospitalizations. The 11 (12%) patients who experienced no bleeding event presented a significantly more restricted SLE phenotype (cutaneous and/or articular). Patients received a mean (range) of 4.2 (1-11) treatment lines. Corticosteroids and HCQ allowed ITPCS overall response in one-third of patients. The median relapse-free survival of rituximab (n = 34), AZA (n = 19), MMF (n = 8), thrombopoietin-receptor agonists (n = 16) and splenectomy (n = 19) were 53, 31.5, 61, 24.5 and 78 months, respectively. Four patients experienced thrombotic events after splenectomy and one occurred under thrombopoietin-receptor agonist treatment. CONCLUSION: SLE-ITCS patients displayed a high rate of haematological abnormalities and MBG patients exhibited higher morbidity. Management of thrombocytopenia was highly heterogeneous and many options seem viable.

Characterisation of a high-risk profile for maternal thrombotic and severe haemorrhagic complications in pregnant women with antiphospholipid syndrome in France (GR2): a multicentre, prospective, observational study.

BACKGROUND: Prospective data about the risks of thrombotic and severe haemorrhagic complications during pregnancy and post partum are unavailable for women with antiphospholipid syndrome. We aimed to assess thrombotic and haemorrhagic events in a prospective cohort of pregnant women with antiphospholipid syndrome. METHODS: This multicentre, prospective, observational study was done at 76 centres in France. To be eligible for this study, women had to have diagnosis of antiphospholipid syndrome; have conceived before April 17, 2020; have an ongoing pregnancy that had reached 12 weeks of gestation; and be included in the study before 18 weeks of gestation. Exclusion criteria were active systemic lupus erythematosus nephropathy, or a multifetal pregnancy. Severe haemorrhage was defined as the need for red blood cell transfusion or maternal intensive care unit admission because of bleeding or invasive procedures, defined as interventional radiology or surgery, to control bleeding. The GR2 study is registered with ClinicalTrials.gov, NCT02450396. FINDINGS: Between May 26, 2014, and April 17, 2020, 168 pregnancies in 27 centres met the inclusion criteria for the study. 89 (53%) of 168 women had a history of thrombosis. The median term at inclusion was 8 weeks gestation. 16 (10%) of 168 women (95%CI 5-15) had a thrombotic (six [4%] women; 95% CI 1-8) or severe haemorrhagic event (12 [7%] women; 95% CI 4-12). There were no deaths during the study. The main risk factors for thrombotic events were lupus anticoagulant positivity at inclusion (six [100%] of six women with thrombosis vs 78 [51%] of 152 of those with no thrombosis; p=0·030) and placental insufficiency (four [67%] of six women vs 28 [17%] of 162 women; p=0·013). The main risk factors for severe haemorrhagic events were pre-existing maternal hypertension (four [33%] of 12 women vs 11 [7%] of 156 women; p=0·014), lupus anticoagulant positivity at inclusion (12 [100%] of 12 women vs 72 [49%] of 146 women; p<0·0001) and during antiphospholipid history (12 [100%] of 12 women vs 104 [67%] of 156 women; p=0·019), triple antiphospholipid antibody positivity (eight [67%] of 12 women vs 36 [24%] of 147 women; p=0·0040), placental insufficiency (five [42%] of 12 women vs 27 [17%] of 156 women; p=0·038), and preterm delivery at 34 weeks or earlier (five [45%] of 11 women vs 12 [8%] of 145 women; p=0·0030). INTERPRETATION: Despite treatment adhering to international recommendations, a proportion of women with antiphospholipid syndrome developed a thrombotic or severe haemorrhagic complication related to pregnancy, most frequently in the post-partum period. Lupus anticoagulant and placental insufficiency were risk factors for these life-threatening complications. These complications are difficult to prevent, but knowledge of the antenatal characteristics associated with them should increase awareness and help physicians manage these high-risk pregnancies. FUNDING: Lupus France, association des Sclérodermiques de France, association Gougerot Sjögren, Association Francophone contre la Polychondrite chronique atrophiante, AFM-Telethon, the French Society of Internal Medicine and Rheumatology, Cochin Hospital, the French Health Ministry, FOREUM, the Association Prix Veronique Roualet, and UCB.

Cardiac Sarcoidosis Is Uncommon in Patients with Isolated Sarcoid Uveitis: Outcome of 294 Cases.

Recently, concerns have been raised about an increased risk of cardiac sarcoidosis in patients with sarcoid uveitis. While cardiac sarcoidosis has a high mortality burden, there is still a lack of precise data on this association. The objective of this study is to describe the frequency and type of cardiac complications associated with sarcoidosis of a large cohort of patients with sarcoid uveitis. We analyzed the cardiac outcomes of a monocentric retrospective cohort of consecutive adults with a diagnosis of sarcoid uveitis between January 2004 and March 2020 in a tertiary French university hospital. A total of 294 patients with a final diagnosis of sarcoid uveitis were included. At final follow-up, seven (2.4%) patients of the cohort had cardiac sarcoidosis. Cardiac sarcoidosis was more frequent among patients with previously reported systemic sarcoidosis (p = 0.008). The prevalence of cardiac sarcoidosis among patients with sarcoid uveitis is low, but patients with previously diagnosed sarcoidosis or those who develop systemic sarcoidosis during follow-up appear to be at increased risk.

CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME AND POSTERIOR OCULAR INVOLVEMENT: Case Series of 11 Patients and Literature Review.

PURPOSE: To describe the posterior ophthalmic manifestations of catastrophic antiphospholipid syndrome. METHODS: Retrospective case series of patients presenting with catastrophic antiphospholipid syndrome and posterior segment ocular manifestations. The main outcomes were the type of posterior segment manifestations at catastrophic antiphospholipid syndrome diagnosis, specifically retinal vascular occlusion, vasculitis, or choroidopathy, and the final best-corrected visual acuity. RESULTS: This study included 23 patients (11 cases treated by the authors and 12 published case reports); 21 (91%) of them female. Their median age at diagnosis was 28 years (range, 16-79 years). Ophthalmologic manifestations were usually bilateral (n = 19, 83%) and involved vascular occlusive retinopathy (n = 17, 74%), choroidopathy (n = 11, 48%), or retinal vasculitis (n = 1, 4%). Final best-corrected visual acuity was not significantly worse than the best-corrected visual acuity at diagnosis (P = 0.16). Retinal vascular occlusions were associated with poorer final visual acuity than choroidopathy (P = 0.002). After a median follow-up of 14 months (range, 2-132 months), nearly half the patients (n = 11, 48%) had permanent vision loss including best-corrected visual acuity of <20/400 for 4 patients. CONCLUSION: Posterior ophthalmic manifestations of catastrophic antiphospholipid syndrome were mainly bilateral retinal vascular occlusion, which had the worst visual prognosis, followed by choroidopathy and retinal vasculitis. Permanent visual loss was common.

Characteristics and risk factors for poor outcome in patients with systemic vasculitis involving the gastrointestinal tract.

BACKGROUND: Gastrointestinal (GI) involvement was described to be a poor prognostic factor in systemic necrotizing vasculitis. Its prognostic significance may vary according to clinical presentation and vasculitis subtype. AIMS: This study investigated risk-factors associated to poor outcome in GI-involvement of vasculitis. METHODS: Patients with systemic vasculitis as defined by the 2012 Chapel Hill Consensus Conference and presenting with GI involvement were retrospectively included. Baseline characteristics, treatments and outcome were recorded. Primary endpoint was a composite of admission to intensive care unit (ICU), emergency surgical procedure, or death. RESULTS: Two hundred and thirteen patients were included. Vasculitis were distributed as follows: 41% IgA vasculitis, 27% ANCA-associated vasculitis, 17% polyarteritis nodosa (PAN), and 15% other vasculitis. Eighty-three (39%) patients fulfilled the composite primary endpoint within 6 months. Predictive factors associated with the primary endpoint included PAN subtype (OR 3.08, 95% CI 1.29-7.34), performance status (OR 1.40, 1.05-1.87), use of morphine (OR 2.51, 0.87-7.24), abdominal guarding (OR 3.08, 1.01-9.37), ileus (OR 2.29, 0.98-5.32), melena (OR 2.74, 1.17-6.42), increased leukocytes (per G/L, OR 1.05, 1.00-1.10), low hemoglobin (per g/dL, OR 0.80, 0.71-0.91) and increased CRP (log mg/L, OR 1.21, 0.94-1.56). A risk prediction model for the achievement of primary endpoint had a very good performance [C-statistics 0.853 (0.810 to 0.895], and for overall survival as well. CONCLUSIONS: Vasculitis presenting with GI involvement have a poor outcome in more than one third of cases. An easy-to-use risk prediction model had a very good performance to predict the admission to ICU, emergency surgical procedure, or death.