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Transplacental passage of maternal anti-SSA and anti-SSB antibodies, potentially associated with maternal autoimmune diseases, can cause neonatal lupus syndrome. Given the paucity of data in this setting, we report short- and long-term outcomes of mothers of offspring with congenital heart block (CHB).This retrospective study included anti-SSA/SSB antibody-positive mothers of fetuses with high-degree CHB and focused on their health status before pregnancy, at CHB diagnosis, and thereafter.We analyzed 215 women with at least 1 pregnancy with CHB. Prior to this diagnosis, only 52 (24%) mothers had been diagnosed with an autoimmune disease, mainly systemic lupus erythematosus (SLE; n = 26, 12%) and Sjögren syndrome (SS; n = 16, 7%). Six more were diagnosed with an autoimmune disease during the index pregnancy. Of the 157 mothers (73%) with no such diagnosis at childbirth, 77 (49%) developed one after a median follow-up of 11 years (range: 21 days to 54 years). By the end of follow-up, 135 women (63%) had an autoimmune disease diagnosis, mainly SLE (n = 54, 25%) and SS (n = 72, 33%). Three patients with SLE had renal involvement, and only 6 (3%) had required an immunosuppressive drug at any point. The symptoms best predicting autoimmune disease development were arthralgia and myalgia (One-quarter of the patients had an autoimmune disease diagnosis at the time of the fetal CHB diagnosis. Nearly half of those without an initial diagnosis progressed during follow-up, most without severe manifestations. Severe diseases such as lupus nephritis were rarely seen, and immunosuppressive drugs were rarely required.

Resume Les maladies auto-immunes systemiques et les rhumatismes inflammatoires chroniques concernent frequemment des femmes jeunes en âge de procreer. Les grossesses sont generalement possibles et les risques fœto-maternels restent acceptables. Il est cependant indispensable que ces femmes soient informees qu’une grossesse pourra etre menee le plus souvent sans complications severes dans le cas ou la conception survient au cours d’une periode de remission. Le projet d’une grossesse doit donc etre aborde regulierement et sa planification est fortement recommandee. Celle-ci est realisee idealement au cours d’une consultation preconceptionnelle afin de rechercher d’eventuelles contre-indications (peu frequentes) et les facteurs de complications obstetricales (complication obstetricale anterieure, presence d’une biologie ou d’un syndrome des antiphospholipides, pathologie active en debut de grossesse, et insuffisance d’organe sequellaire d’une poussee anterieure) afin d’optimiser la prise en charge. Les complications obstetricales les plus frequentes sont les pertes fœtales et/ou les consequences d’une insuffisance placentaire. La presence d’anticorps anti-SSA et/ou anti-SSB expose a un risque faible de bloc auriculoventriculaire fœtal. Les traitements doivent etre adaptes avant la conception afin, d’une part, de limiter le risque de poussee en debut de grossesse et, d’autre part, d’interrompre ou remplacer les medicaments teratogenes. Enfin, le rythme et le lieu de la surveillance de cette future grossesse seront definis de maniere multidisciplinaire et expliques a la patiente a cette occasion.

ObjectiveTo investigate outcome and course of pregnancies in women with axial spondyloarthritis (axSpA) in a pooled data analysis of pregnancy registries in rheumatology.MethodsProspectively followed women with axSpA, fulfilling ASAS classification criteria and for whom a pregnancy outcome was reported, were eligible for the analysis. Anonymised data of four registries was pooled. Rates of adverse pregnancy outcomes were calculated. Systemic inflammation, disease activity and treatment patterns with tumour necrosis factor inhibitor (TNFi) before, during and after pregnancy were analysed.ResultsIn a total of 332 pregnancies from 304 axSpA women, 98.8% of the pregnancies resulted in live birth. Mean maternal age was 31 years and disease duration 5 years. Most of these patients received pre-conception counselling (78.4%). Before pregnancy, 53% received TNFi treatment, 27.5% in first and 21.4% in third trimester. Pregnancy and neonatal outcomes were favourable with rates of 2.2% for pre-eclampsia, 4.9% for preterm birth, 3.1% for low birth weight and 9.5% for small for gestational age. Neonates were delivered by caesarean section in 27.7% of pregnancies, of which 47.4% were emergencies. Pooled mean CRP was 4 mg/L before conception peaking in the second trimester at 9.4 mg/L. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was below 4 at all time-points.ConclusionsPooled rates of most outcomes were better than what had been reported in the literature and within expected rates of those reported for the general population. Pre-conception counselling, planned pregnancies and a tight management in expert centres applying a tailored treatment approach may have contributed to the favourable pregnancy outcomes.

Objective HCQ is an essential medication in SLE, proven to lengthen survival and reduce flares. Its use, however, is limited by its rare but severe ophthalmological complications. Here, we aimed to analyse factors associated with HCQ retinopathy including HCQ blood levels. Methods This case–control study compared SLE patients with and without HCQ retinopathy, defined by abnormal results for at least two of the following ophthalmological tests: automated visual fields, spectral-domain optical coherence tomography (SD-OCT), multifocal electroretinogram (mfERG) and fundus autofluorescence. We compared clinical and laboratory findings to assess risk factors for HCQ retinopathy. Results The study included 23 patients with confirmed retinopathy (cases) and 547 controls. In the univariate analysis, age (P Conclusion SLE patients on HCQ should be closely monitored for retinopathy, especially those from the West Indies or sub-Saharan Africa, or with renal insufficiency, longer HCQ intake or a high cumulative dose. Although reducing the daily dose of HCQ in patients with persistently high HCQ blood levels seems logical, these concentrations were not associated with retinopathy in this study with controls adherent to treatment.

Objectives The specific roles of remission status, lupus low disease activity state (LLDAS), and damage accrual on the prognosis of pregnancies in women with SLE are unknown. We analysed their impact on maternal flares and adverse pregnancy outcomes (APOs). Methods We evaluated all women (≥18 years) with SLE enrolled in the prospective GR2 study with an ongoing singleton pregnancy at 12 weeks (one pregnancy/woman). Several sets of criteria were used to define remission, disease activity and damage. APOs included: foetal/neonatal death, placental insufficiency with preterm delivery and small-for-gestational-age birth weight. First trimester maternal and disease features were tested as predictors of maternal flares and APOs. Results The study included 238 women (98.3% on hydroxychloroquine (HCQ)) with 230 live births. Thirty-five (14.7%) patients had at least one flare during the second/third trimester. At least one APOs occurred in 34 (14.3%) women. Hypocomplementemia in the first trimester was the only factor associated with maternal flares later in pregnancy (P=0.02), while several factors were associated with APOs. In the logistic regression models, damage by SLICC-Damage Index [odds ratio (OR) 1.8, 95% CI: 1.1, 2.9 for model 1 and OR 1.7, 95% CI: 1.1, 2.8 for model 2] and lupus anticoagulant (LA, OR 4.2, 95% CI: 1.8, 9.7 for model 1; OR 3.7, 95% CI: 1.6, 8.7 for model 2) were significantly associated with APOs. Conclusion LA and damage at conception were predictors of APOs, and hypocomplementemia in the first trimester was associated with maternal flares later in pregnancy in this cohort of pregnant patients mostly with well-controlled SLE treated with HCQ. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT02450396.

Introduction Data about the predictors of adverse neonatal outcome in pregnant women with antiphospholipid syndrome (APS) are sparse. The main study on this subject is the prospective American study PROMISSE on 144 carriers of antiphospholipid antibodies.1 We report the first results of the French study, GR2. Methods Inclusion criteria were: (1) an ongoing pregnancy at 12 weeks of gestation (WG), (2) conceived before May 2018, (3) of a woman with APS.2 Exclusion criteria were proteinuria (ratio >1 g/g), serum creatinine >100 µmol/L, and multifetal pregnancy. The composite primary outcome included an intrauterine fetal death (IUFD), a neonatal death, placental insufficiency (fetal growth restriction, preeclampsia, HELLP syndrome, and/or placental abruption) leading to a delivery ≤34 WG, and/or a small for gestational age (SGA) ≤3rd percentile. Results We analysed 119 pregnancies in 119 patients: 53% thrombotic and 47% obstetric only APS; 60% had lupus anticoagulant (LA) and 26% associated SLE. Treatment included aspirin (99%), heparin (98%, in the therapeutic range for 50%), and hydroxychloroquine (62%). The primary outcome was observed in 14% of pregnancies: 3% IUFD, 8% delivery ≤34WG due to placental insufficiency and/or 5% of SGA (and no neonatal death). It was observed in 20% of the pregnancies with LA compared with 7% for women negative for LA (P=0.096). This outcome did not differ according to anticardiolipin or antiβ2GP1 antibody status, or prior thrombosis (14%, versus 14% for women with only obstetric APS). There was a trend toward more adverse neonatal outcomes in case of prior arterial thrombosis (29% versus 12%, P=0.07). The rate of adverse neonatal outcomes did not differ among the women with or without associated SLE (29% versus 26%, P=0.77). In multivariate analysis, independent features associated with pregnancy failure were: in a serological model, LA positive status (ORa=8.5, 95%CI[1.0–71.5]) and in a serological and clinical model, ‘non-white’ skin colour (ORa=6.1, 95%CI[1.1–34.7]). Conclusion The rate of adverse neonatal outcomes tended to be lower than in the PROMISSE study (14% versus 19%), although the women included here were theoretically more severe (definite APS). One potential explanation might be that our patients were all treated. In keeping with the PROMISSE study, LA and skin colour were the main predictors of neonatal outcome. Acknowledgement Fondation pour la Recherche Medicale (M2R201806006403) References Lockshin MD, et al. Arthritis Rheum. 2012; 64;2311–8. Miyakis S, et al. J Thromb Haemost. 2006; 4 ;295–306. Andreoli L, et al. Ann Rheum Dis. 2017; 76; 476–85.

Purpose The purpose of this study was to evaluate the safety of antithrombotic treatments prescribed during pregnancy in patients with antiphospholipid syndrome (APS). Methods This international, multicenter study included two cohorts of patients: a retrospective French cohort and a prospective US cohort (PROMISSE study). Inclusion criteria were (1) APS (Sydney criteria), (2) live pregnancy at 12 weeks of gestation (WG) with (3) follow-up data until six weeks post-partum. According to APS standard of care, patients were treated with aspirin and/or low-molecular weight heparin (LMWH) at prophylactic (pure obstetric APS) or therapeutic doses (history of thrombosis). Major bleeding was defined as abnormal blood loss during the pregnancy and/or post-partum period requiring intervention for hemostasis or transfusion, or during the peripartum period greater than 500 mL and/or requiring surgery or transfusion. Other bleeding events were classified as minor. Results Two hundred and sixty-four pregnancies (87 prospectively collected) in 204 patients were included (46% with history of thrombosis, 23% with associated systemic lupus). During pregnancy, treatment included LMWH ( n = 253; 96%) or low-dose aspirin ( n = 223; 84%), and 215 (81%) patients received both therapies. The live birth rate was 89% and 82% in the retrospective and prospective cohorts, respectively. Adverse pregnancy outcomes occurred in 28% of the retrospective cohort and in 40% of the prospective cohort. No maternal death was observed in either cohort. A combined total of 45 hemorrhagic events (25%) occurred in the retrospective cohort, but major bleeding was reported in only six pregnancies (3%). Neither heparin nor aspirin alone nor combined therapy increased the risk of hemorrhage. We also did not observe an increased rate of bleeding in the case of a short interval between last LMWH (less than 24 hours) or aspirin (less than five days) doses and delivery. Only emergency Caesarean section was significantly associated with an increased risk of bleeding (odds ratio (OR) 5.03 (1.41–17.96); p=.016). In the prospective cohort, only one minor bleeding event was reported (vaginal bleeding). Conclusion Our findings support the safety of antithrombotic therapy with aspirin and/or LMWH during pregnancy in high-risk women with APS, and highlight the need for better treatments to improve pregnancy outcomes in APS. PROMISSE Study ClinicalTrials.gov identifier: NCT00198068.

Background Dilated cardiomyopathy (DCM), a well-known complication of cardiac neonatal lupus, is associated with high mortality rate. Its risk factors remain unclear. Methods We analyzed occurrence of postnatal DCM among children with high-degree congenital heart block (CHB) and mothers with anti-SSA and/or anti-SSB antibodies. Results Among 187 neonates with CHB, 35 (18.8%, one missing data) had DCM and 22 (11.8%) died during a median follow-up of 7years [range: birth–36years]. On multivariate analysis, factors associated with postnatal DCM were in utero DCM ( P =0.0199; HR=3.13 [95% CI: 1.20–8.16]), non-European origin ( P =0.0052; HR=4.10 [95% CI: 1.81–9.28]) and pacemaker implantation ( P =0.0013; HR=5.48 [95% CI: 1.94–15.47]). Postnatal DCM could be categorized in two subgroups: neonatal DCM (n=13, diagnosed at a median age of 0day [birth–4days]) and late-onset DCM (n=22, diagnosed at a median age of 15.2months [3.6months–22.8years]). Factors associated with neonatal DCM were in utero DCM, hydrops, endocardial fibroelastosis and pericardial effusion, whereas those associated with late-onset DCM were non-European origin, in utero mitral valve insufficiency, and pacemaker implantation. Fluorinated steroids showed no protective effect against late-onset DCM ( P =0.27; HR=1.65 [95% CI: 0.63–4.25]). Probability of survival at 10years was 23.1% for newborns diagnosed neonatally with DCM, 53.9% for those who developed late-onset DCM, and 98.6% for those without DCM. Conclusion Neonatal and late-onset DCM appear to be two different entities. None of the known risk factors associated with neonatal DCM predicted late-onset DCM. Long-term follow-up of cardiac function is warranted in all children with CHB.

Objective.To compile and assess data about complication and success rates forin vitrofertilization (IVF) of women with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). To date, such data are sparse.Methods.This retrospective study described women with SLE and/or APS who have had at least 1 IVF cycle.Results.Thirty-seven women with SLE (n = 23, including 8 with antiphospholipid antibodies), SLE with APS (n = 4), or primary APS (n = 10) underwent 97 IVF procedures. For 43% of cases, the infertility was female in origin, for 19% male, 14% mixed, and 24% unexplained. No women had premature ovarian insufficiency because of cyclophosphamide. Median age at IVF was 34 years (range 26–46). The median number of IVF cycles was 2.6 (1–8). Patients were treated with hydroxychloroquine (72%), steroids (70%), azathioprine (3%), aspirin (92%), and/or low molecular weight heparin (62%). There were 27 (28%) pregnancies, 23 live births among 26 neonates (3 twin pregnancies), 2 miscarriages, and 2 terminations for trisomy 13 and 21. Six spontaneous pregnancies occurred during the followup. Finally, 26 women (70%) delivered at least 1 healthy child. Complications occurred in or after 8 IVF cycles (8%): SLE flares in 4 (polyarthritis in 3 and lupus enteritis in 1) and thromboembolic events in 4 others. One SLE flare was the first sign of previously undiagnosed SLE. Poor treatment adherence was obvious in 2 other flares and 2 thromboses. No ovarian hyperstimulation syndrome was reported.Conclusion.These preliminary results confirm that IVF can be safely and successfully performed in women with SLE and/or APS.

Cardiac neonatal lupus syndrome is due to anti-SSA or SSB antibodies and mainly includes congenital heart block (CHB) and dilated cardiomyopathy (DCM). Its optimal management is still debated. We report a large series of autoimmune high degree CHB.Inclusion criteria in this retrospective study were fetuses or neonates with high-degree CHB associated with maternal anti-SSA/SSB antibodies.214 CHB were included: 202 detected in utero at a median term of 23 weeks' gestation (WG) [range 16 to 39 WG] and 12 neonatal cases diagnosed at a median age of 0 days [range birth to 8 days]. The 214 cases of CHB included 202 (94.4%) third-degree CHB, 8 (3.7%) second-degree CHB, and 4 (1.9%) intermittent CHB. In multivariate analysis, the factors associated with feto-neonatal deaths (15.7%) were hydrops (p0.001; hazard ratio [HR] 12.4 [95% confidence interval (95%CI) 4.7-32.7]) and prematurity (p=0.002; HR 17.1 [95%CI 2.8-103.1]). During a median follow-up of 7 years [birth to 36 years], 148 of 187 children born alive (79.1%) had a pacemaker, 35 (18.8%, one missing data) had DCM, and 22 (11.8%) died. In multivariate analysis, factors associated with child death were in utero DCM (p=0.0157; HR 6.37 [95%CI: 1.25-32.44]), postnatal DCM (p0.0001; HR 227.58[95%CI: 24.33-2128.46]) and pacemaker implantation (p=0.0035; HR 0.11[95%CI: 0.02-0.51]). The use of fluorinated steroids was neither associated with survival nor with regression of 2nd degree CHB.In this second largest series of CHB, we confirm some of the previous results. We were unable to find data supporting the routine use of in utero fluorinated steroids.

Resume Propos L’objectif de ce travail etait de proposer des recommandations relatives aux modalites de depistage et de prise en charge des facteurs de risque cardiovasculaire au cours du lupus systemique. Methodes Trente-neuf experts internistes, rhumatologues ou nephrologues francais, membres du reseau des centres de reference et de competence du lupus systemique ont pris part a un vote visant a retenir ou non des recommandations preparees par un groupe de travail a partir d’une revue de la litterature. Resultats Les experts ont souligne que les facteurs de risque cardiovasculaires modifiables doivent etre recherches au moins annuellement au cours du lupus systemique. La prescription d’une statine en prevention primaire depend du taux de LDL-cholesterol et du nombre de facteurs de risque cardiovasculaires, en considerant le lupus systemique comme un facteur de risque cardiovasculaire supplementaire. En prevention secondaire, les experts s’accordent a proposer une cible de LDL-cholesterol Conclusions Ces recommandations vont permettre d’ameliorer et d’homogeneiser la pratique des differents medecins francais impliques dans la prise en charge du lupus systemique. L’actualisation de ces recommandations pourra etre ulterieurement envisagee, en fonction des nouvelles donnees publiees.

Liver disease can be observed in pregnant women whether or not related to pregnancy. Liver disorders can be revealed by pruritus, vomiting, jaundice or abnormal liver blood tests during pregnancy. These liver manifestations can lead to the diagnosis of liver disease specifically associated to pregnancy as intrahepatic pregnancy, intrahepatic cholestasis of pregnancy, Hyperemesis gravidarum, acute fatty liver of pregnancy and preeclampsia-induced liver injury. Pregnancy may also be a risk factor for other liver diseases coincident with pregnancy as viral hepatitis, thrombosis, drug toxicity or gallstone. Finally, pre-existing liver disease must be taken into account given the risk of fœto-maternal transmission risk as well as the risk of decompensation of underlying cirrhosis secondary to the hemodynamic changes caused by pregnancy. The aim of this revue is to perform an update on the various situations that can be observed, the principles of management of these liver diseases, in order to reduce the risk of complications and to ensure the best maternal and fetal prognosis.

RésuméLa survenue d’une grossesse au cours du lupus systémique est une situation fréquente qui reste associée à une morbi-mortalité maternelle et fœtale plus importante que dans la population générale. Les complications incluent les poussées lupiques, les complications obstétricales (pertes fœtales, retard de croissance in utero, pré-éclampsie, prématurité) et le lupus néonatal. Une biologie ou un syndrome des antiphospholipides augmente nettement le risque de complications obstétricales. L’amélioration de la prise en charge de ces grossesses est conditionnée par leur planification systématique, idéalement au cours d’une consultation pré-conceptionnelle, et par une prise en charge multidisciplinaire avec une collaboration étroite entre interniste/rhumatologue, obstétricien et anesthésiste. L’absence d’activité du lupus, un traitement compatible avec la grossesse adapté aux antécédents et aux risques ainsi qu’une surveillance régulière sont les principaux éléments permettant une issue favorable à ces grossesses à risque. Cette revue a pour objectif de proposer une mise au point sur la prise en charge actuelle de la grossesse au cours du lupus systémique ou du syndrome des antiphospholipides afin de limiter le risque de complications et d’assurer le meilleur pronostic tant maternel que fœtal.AbstractPregnancy in systemic lupus erythematosus patients is a common situation that remains associated with higher maternal and fetal mortality/morbidity than in the general population. Complications include lupus flares, obstetrical complications (fetal loss, in utero growth retardation, prematurity) and neonatal lupus syndrome. The association with antiphospholipid antibodies or antiphospholipid syndrome increases the risk of obstetrical complications. Improving the care of these pregnancies depends upon a systematic pregnancy planning, ideally during a preconception counseling visit and a multidisciplinary approach (internist/rheumatologist, obstetrician and anesthetist). The absence of lupus activity, the use of appropriate medications during pregnancy adjusted to the patient's medical history and risk factors, and a regular monitoring are the best tools for a favorable outcome for these high-risk pregnancies. The aim of this review article is to perform an update on the medical care of pregnancy in systemic lupus erythematosus or antiphospholipid syndrome to reduce the risk of complications and to ensure the best maternal and fetal prognosis.

Neonatal lupus syndrome is associated with transplacental passage of maternal anti-SSA/Ro and anti-SSB/La antibodies. Children display cutaneous, hematological, liver or cardiac features. Cardiac manifestations include congenital heart block (CHB); endocardial fibroelastosis and dilated cardiomyopathy. The prevalence of CHB in newborns of anti-Ro/SSA positive women with known connective tissue disease is between 1 and 2% and the risk of recurrence is around 19%. Skin and systemic lesions are transient, whereas CHB is definitive and associated with significant morbidity and a mortality of 18%. A pacemaker must be implanted in 2/3 of cases. Myocarditis may be associated or appear secondly. Mothers of children with CHB are usually asymptomatic or display Sjogren's syndrome or undifferentiated connective tissue disease. In anti-Ro/SSA positive pregnant women, fetal echocardiography should be performed at least every 2 weeks from the 16th to 24th week gestation. An electrocardiogram should be performed for all newborn babies. The benefit of fluorinated corticosteroid therapy for CHB detected in utero remains unclear. Maternal use of hydroxychloroquine may be associated with a decreased recurrent CHB risk in a subsequent offspring. A prospective study is actually ongoing to confirm these findings.

Fertility is not impaired in systemic lupus erythematosus or antiphospholipid syndrome, but, similarly to the general population, these patients may undergo in vitro fertilization. This type of treatment increases the risk of lupus flare, thrombosis, and ovarian hyperstimulation syndrome. This review will focus on in vitro fertilization in systemic lupus erythematosus or antiphospholipid syndrome. Literature data are relatively scant with only 3 reported studies. The first one included 17 patients and 63 cycles of induction ovulation/in vitro fertilization leading to 25 % of lupus flare, no thrombosis, and 3 % of ovarian hyperstimulation syndrome. The second study included 10 patients and 40 cycles of in vitro fertilization showing 31 % of lupus flare, no thrombosis and no ovarian hyperstimulation syndrome. The last one included 34 patients and 83 procedures of in vitro fertilization leading to 8 % of flares, 5 % of thrombosis and no ovarian hyperstimulation syndrome. Interestingly, in this last study, half of the complications were explained by poor adherence to treatment. These data are reassuring but it is important to remember that in vitro fertilization should be scheduled and carefully supervised in the same way as the high-risk pregnancies occurring in these patients.

The efficacy of antimalarials, especially hydroxychloroquine (HCQ), in preventing systemic lupus erythematosus (SLE) flares is well demonstrated. However, many studies show that the percentage of SLE patients treated with HCQ remains low. By blocking the toll-like receptor 7 and 9 in plasmacytoid dendritic cells, HCQ inhibits interferon-alpha production which plays a crucial role in SLE pathogenesis. In addition to reducing damage accrual in SLE patients, HCQ appears to protect against the occurrence of diabetes, thrombotic events, and dyslipidemia. As a consequence, some studies have suggested that HCQ, which is inexpensive, has a protective effect on survival in SLE patients. Thanks to the pharmacokinetic properties of HCQ (long half-life) and to the availability of its blood assay, very low or undetectable blood HCQ concentrations are a valuable marker of non-adherence to treatment, thus adding a new benefit to HCQ prescriptions. The main side effect of HCQ is retinal toxicity. This complication is very rare, but may be potentially severe, thus requiring regular screening. Retinal toxicity remains the only absolute contra-indication of HCQ in adult SLE patients. Other contra-indications are few and rare. During pregnancy and breast-feeding, HCQ continuation is not only allowed but recommended. In conclusion, the risk/benefit ratio of HCQ is excellent. Many now believe that all SLE patients should be offered this treatment.

Resume Propos Les neoplasies myeloproliferatives (NMP) sont des desordres hematologiques caracterises par l’expansion clonale d’une ou plusieurs lignees medullaires. Les complications renales sont rares et se manifestent principalement par un tableau d’insuffisance renale aigue. L’atteinte glomerulaire est quant a elle exceptionnelle Methodes Nous decrivons ici une serie retrospective multicentrique de huit cas de glomerulopathie (GP) associee a une NMP Resultats Toutes les GP se sont manifestees par une proteinurie majeure regulierement accompagnee d’un syndrome nephrotique et d’œdemes des membres inferieurs. L’histologie est surtout caracterisee par des lesions de hyalinose segmentaire et focale associee a une augmentation de la cellularite mesangiale. La physiopathologie reste non elucidee mais il semble que le platelet-derived growth factor (PDGF) et le transforming growth factor-β (TGF-β), qui jouent un role central dans les NMP, puissent etre impliques. La majorite des patients ont ete traites par blocage du systeme renine-angiotensine. Mais l’evolution se fait generalement vers l’insuffisance renale chronique Conclusion La surveillance de la proteinurie au cours du suivi des NMP permettrait un diagnostic plus precoce de cette complication. Des etudes complementaires a plus grande echelle sont necessaires afin, d’une part, de preciser les mecanismes physiopathologiques mis en jeu et, d’autre part, de codifier la prise en charge specifique de ces complications

Resume La consultation preconceptionnelle est une des cles du succes de la grossesse chez les femmes atteintes d’une maladie auto-immune ou systemique, notamment un lupus systemique ou un syndrome des antiphospholipides. Cette consultation, idealement a proposer a toutes les patientes suivies pour une maladie systemique, permet de donner le feu vert pour debuter une grossesse ou d’expliquer pourquoi ce projet doit etre retarde, d’anticiper certains problemes, de proposer une information complete au couple, d’organiser une prise en charge multidisciplinaire, d’adapter les traitements et de verifier la validite des vaccinations. La generalisation de ce type de consultation devrait permettre de reduire les risques fœto-maternels chez ces jeunes femmes, et d’ameliorer encore le pronostic de ces grossesses.

Resume Introduction L’exploration des pericardites recidivantes permet la decouverte d’une etiologie specifique dans seulement 15 a 20 % des cas. Le mesotheliome pericardique primitif (MPP) est l’une d’entre elles et reste rare. Son diagnostic n’est etabli avec certitude que dans 10 a 20 % des cas avant autopsie. Il repose sur des arguments a la fois histologiques et immunohistochimiques. La mediane de survie apres diagnostic est d’environ six mois mais semble s’ameliorer avec le pemetrexed. Observation Nous rapportons l’observation d’une femme de 64 ans chez laquelle des biopsies pericardiques repetees ont ete necessaires pour l’obtention du diagnostic de MPP ; l’histologie initiale etant une hyperplasie mesotheliale benigne. Conclusion Cette observation souligne la necessite de repeter les biopsies pericardiques en cas d’evolution defavorable d’une pericardite.

Key points IgG4 related disease (IgG4 RD) was first reported as autoimmune pancreatitis then it was established as a systemic disorder characterised by high blood level of IgG4 and fibrosis with rich plasmocytes IgG4+ in almost all organs. IgG4 RD is very sensitive to corticosteroid therapy. IgG4 RD has a high prevalence in eastern countries. Numerous articles on this topic are published and new diagnostic criteria are regularly established. The autoimmune or allergic mechanism of IgG4 RD is still a matter of debate. Interestingly, IgG4 subclass of antibody has anti-inflammatory features. IgG4 RD is not yet very well characterised in western countries. Whether IgG4 is involved in IgG4 RD, pathophysiology is to be defined. IgG4 RD spontaneously regresses in some cases so indications of treatment are not already well clear.

Objective. Immunoglobulin-G4-(IgG4-) related disease (IgG4 RD) is a fibrosing process characterized by a significant infiltration of IgG4-secreting plasma cells. IgG4 RD can affect almost all organs including salivary glands. Whether IgG4 RD plays a role in the development of sicca syndrome and particularly dry mouth syndrome remains to be investigated.Methods. We conducted a monocentric cohort study for two years to search for IgG4 RD features in patients with dry mouth syndrome using immunostainings of labial salivary gland specimens with anti-IgG4 antibody.Results. Among 60 patients presenting with dry mouth syndrome who underwent labial salivary gland biopsy, 18 showed positive immunostaining with the anti-IgG4 antibody including 4 patients with typical systemic IgG4 RD. Five also fulfilled criteria for Sjögren's syndrome.Conclusion. These findings suggest that clinical forms of IgG4 RD salivary involvement without salivary swelling may occur. This salivary involvement is probably overlooked in everyday practice and could represent a mild form of IgG4 RD.

Mendelian and complex autoinflammatory disorders frequently manifest as recurrent abdominal pain and fever. Diagnosis may be difficult and scant data are available about the interest of 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in such conditions, particularly aseptic abscesses (AA).We analyzed five cases of AA in which FDG-PET/CT was performed at diagnosis (n = 2) and after a suspected relapse (n = 5). Follow-up FDG-PET/CT was performed in two patients 9 days and 6 weeks after the initiation of oral corticosteroids.FDG-PET/CT showed intense uptake foci in the abdominal lymph nodes (n = 4), liver (n = 2) and spleen (n = 4) before treatment. A marked metabolic response was observed while patients were being treated. In a relapsing patient with abdominal pain but no raised CRP, although CT scan was unchanged, abnormal uptake of FDG was observed. By contrast, some lesions previously observed on CT scan displayed no fixation on new FDG-PET/CT and were suggestive of sequelae in three patients.Although nonspecific, FDG-PET/CT may be an interesting tool for the diagnosis and management of recurrent and febrile abdominal pain in AA. At the time of relapse, it can differentiate between a sequela of previous flares and a new localization. It can be used for whole-body screening to look for other asymptomatic disease localizations.

Resume Introduction La maladie des griffes du chat se manifeste sous la forme d’adenites evoluant dans la majorite des cas spontanement vers la guerison. Nous rapportons deux observations de maladie des griffes du chat avec atteinte pretragienne survenant chez les sujets immunocompetents. Observations Observation 1 : un homme de 28 ans consultait pour une tumefaction cervicale gauche d’apparition recente, avec secondairement une paralysie faciale peripherique et une cytolyse hepatique. Les serologies des hepatites virales, EBV, CMV, VIH, toxoplasmose etaient negatives. La biopsie exerese ganglionnaire retrouvait une lymphadenite granulomateuse et la PCR Bartonella henselae etait positive. Sous doxycycline pendant trois mois, associe a de la rifampicine pendant 15 jours, l’atteinte hepatique disparaissait et la paralysie faciale regressait partiellement. Observation 2 : un homme de 17 ans consultait pour une tumefaction parotidienne droite associee a des adenopathies cervicales posterieures, avec fievre et sueurs profuses. Un volumineux ganglion pretragien droit avec remaniement necrotique etait visible au scanner. La PCR B. henselae sur le liquide de cytoponction ganglionnaire etait positive. L’evolution etait favorable apres un drainage chirurgical et l’echec d’un traitement par macrolides. Conclusion La localisation pretragienne de la maladie des griffes du chat est rare. Cette topographie doit etre connue et necessiter la recherche d’un contact avec un chat apres exclusion d’une localisation tumorale parotidienne, d’un lymphome ou d’une tuberculose. Le diagnostic repose sur la PCR B. henselae . L’evolution est souvent spontanement favorable mais un traitement chirurgical peut etre necessaire.

A causal link has long been described between estrogen and systemic lupus erythematosus activity. Contraceptive and pregnancy management is now common for lupus patients, but pregnancy continues to be associated with higher maternal and fetal mortality/morbidity in systemic lupus erythematosus patients than among the general population. Potential complications include lupus flares, obstetric complications (fetal loss, in utero growth retardation, premature birth) and neonatal lupus syndrome. Association with antiphospholipid antibodies or antiphospholipid syndrome increases the risk of obstetric complications. Anti-SSA and/or anti-SSB antibodies put fetuses at risk for neonatal lupus. Improving the outcome of such pregnancies depends upon optimal systematic planning of pregnancy at a preconception counseling visit coupled with a multidisciplinary approach. Absence of lupus activity, use of appropriate medication during pregnancy based on the patient's medical history and risk factors, and regular monitoring constitute the best tools for achieving a favorable outcome in such high-risk pregnancies. The aim of this review is to provide an update on the management of contraception and pregnancy in systemic lupus erythematosus, cutaneous lupus and/or antiphospholipid syndrome in order to reduce the risk of complications and to ensure the best maternal and fetal prognosis.

Introduction La prise en charge de la grossesse au cours du syndrome des antiphospholipides (SAPL) est complexe et reste principalement empirique. L’objectif de notre etude etait d’evaluer le benefice et les risques des traitements antithrombotiques conventionnels prescrits lors de la grossesse dans une large cohorte de patientes atteintes d’un SAPL. Notre objectif secondaire etait d’identifier les facteurs de risques associes a un pronostic obstetrical defavorable. Patients et methodes Dans cette etude multicentrique internationale, les grossesses evolutives a 12 semaines d’amenorrhees (SA) survenues chez des patientes ayant un SAPL connu (criteres de Sydney), ont ete incluses et suivies jusqu’a six semaines du post-partum. Les donnees ont ete recueillies (1) a partir d’une etude prospective multicentrique americaine et (2) a partir des bases de donnees de quatre centres hospitaliers francais. Les complications obstetricales attribuables au SAPL etaient definies par la survenue : (i) d’une mort fœtale in utero (MFIU) ou (ii) d’un retard de croissance intra-uterin ≤ 5e percentile (RCIU) ou (iii) d’un accouchement premature avant 36 SA sans autre cause retrouvee ou (iv) d’une pre-eclampsie et/ou d’un syndrome HELLP. Resultats Un total de 264 grossesses (chez 204 patientes) ont ete incluses, dont 87 prospectivement. Dans 51 % des grossesses, les patientes avaient une forme thrombotique de SAPL et dans 25 % des cas, les patientes avaient un lupus systemique associe. L’heparine a ete prescrite au cours de 96 % des grossesses (n = 253) et l’aspirine faible dose dans 84 % des grossesses (n = 223). Quatre-vingt-six pour cent des grossesses ont donne naissance a un enfant vivant, sans aucun deces maternel. Les complications obstetricales du SAPL ont ete observees dans 32 % des cas, principalement au cours du 2nd trimestre de grossesse : 11 % de MFIU, 11 % de RCIU, 18 % de pre-eclampsie/HELLP/prematurite. Au cours de ces 264 grossesses, 13 thromboses maternelles ont ete observees (6 thromboses veineuses profondes, 1 embolie pulmonaire, 2 necroses hemorragiques des surrenales, 3 syndromes catastrophiques des antiphospholipides, 1 infarctus splenique) et 46 evenements hemorragiques, avec un saignement majeur dans 2 % des cas (3 hemorragies de la delivrance, 2 reprises chirurgicales pour hematome intra-abdominal, 1 embolisation de l’artere uterine). En analyse multivariee, les facteurs de risque de complication obstetricale etaient un index de masse corporel eleve et la presence d’un anticoagulant circulant lupique. A l’inverse, la prescription d’aspirine (mais pas celle d’heparine) etait associee a une diminution significative de ce risque (odds ratio : 0,34 ; 95 % IC : 0,15–0,78 ; p = 0,01). Le risque hemorragique n’etait pas associe a la prescription d’aspirine ou d’heparine, ni a la duree d’arret de l’aspirine avant l’accouchement (donnees non disponibles dans la cohorte americaine). Conclusion Dans cette large cohorte, nous avons observe un taux eleve de complications obstetricales du SAPL malgre une prise en charge therapeutique conforme aux recommandations. Nos resultats suggerent un benefice clinique important de l’aspirine sans augmentation du risque hemorragique et sont donc en faveur de sa prescription tout au long de la grossesse chez ces patientes.

(2014). Efficacy of Il-1β blockade in refractory aseptic abscesses syndrome. Modern Rheumatology: Vol. 24, No. 1, pp. 217-219.

Context: Cyclophosphamide is used for renal and major extrarenal involvement in systemic lupus erythematosus (SLE) and is associated with a risk of premature ovarian failure. There are no data available about the relation between anti-Müllerian hormone (AMH) serum levels and the probability of subsequent pregnancy in SLE patients. Objective: We analyzed AMH levels and the probability of pregnancy in SLE women exposed to cyclophosphamide. Design and Setting: We conducted a matched cohort study in referral centers for SLE. Patients: Fifty-six cyclophosphamide-exposed SLE women younger than 40 years of age and 56 control SLE women matched for age within 6 months participated in the study. Main Outcome Measures: AMH was measured in samples from the PLUS study (ClinicalTrials.gov no. NCT00413361). All patients were interviewed in May 2012 regarding their obstetric status. Results: The mean age ± SD of the 112 patients was 31.6 ± 5.8 years. The mean AMH level was low (1.21 ± 1.01 ng/mL) and was significantly lower in patients exposed to cyclophosphamide (P = .03) and in patients older than 30 years (P = .02). During a median follow-up (interval between sampling and the interview) period of 4.2 (range, 2.5–4.8) years, 38 patients sought to become pregnant, and 32 (84.2%) succeeded. In the univariate analysis, the risk of failure was associated with cumulative cyclophosphamide dose (P = .007) and older age (P = .02), but not with AMH. Conclusion: We confirmed that AMH levels are low in SLE patients and decrease significantly with age and cyclophosphamide exposure. Nonetheless, the risk of failure to conceive was low and was predicted by cyclophosphamide exposure and age, but not by AMH levels.

International audience; Adherence is defined as "the extent to which a person's behaviour coincides with medical or health advice." Poor adherence to therapeutic regimens is a common and expensive problem in patients with chronic diseases including systemic lupus erythematosus (SLE) and is associated with a higher risk of flares, morbidity, hospitalisations and poor renal outcome. Non-adherence to the treatment is multifactorial for most patients and varies according to unintentional or intentional patterns. The rates of non-adherence in SLE patients range from 3% to 76% depending on the assessment methods, which are all subject to limitations. Indeed, poor adherence to therapeutic regimens is difficult to evaluate. Two studies have shown that undetectable blood hydroxychloroquine (HCQ) concentration may be a simple, objective and reliable marker of non-adherence in SLE patients. The accurate diagnosis of non-adherence may prevent one from incorrectly interpreting disease manifestations as a lack of response. It may then avoid an unnecessary or even dangerous treatment escalation.

IgG4 related disease (IgG4 RD) was first reported as autoimmune pancreatitis then it was established as a systemic disorder characterised by high blood level of IgG4 and fibrosis with rich plasmocytes IgG4+ in almost all organs. IgG4 RD is very sensitive to corticosteroid therapy. IgG4 RD has a high prevalence in eastern countries. Numerous articles on this topic are published and new diagnostic criteria are regularly established. The autoimmune or allergic mechanism of IgG4 RD is still a matter of debate. Interestingly, IgG4 subclass of antibody has anti-inflammatory features. IgG4 RD is not yet very well characterised in western countries. Whether IgG4 is involved in IgG4 RD, pathophysiology is to be defined. IgG4 RD spontaneously regresses in some cases so indications of treatment are not already well clear.

Objective.Maternal anti-SSA/Ro or anti-SSB/La antibodies are associated with neonatal lupus erythematosus syndrome (NLES), especially congenital heart block (CHB), which may be associated with severe endocardial fibroelastosis (EFE) and dilated cardiomyopathy (DCM). A few reports have described severe EFE without CHB associated with anti-SSA/Ro antibodies, with a poor prognosis. EFE has also been observed in biopsies of DCM that had been considered idiopathic. These points, considered in association with 5 unusual cases of mild EFE, led us to consider the relationship between underrecognized cases of isolated autoantibody-associated EFE and DCM that had been considered idiopathic.Methods.We analyzed 5 cases of EFE diagnosed in utero (n = 4) or after birth (n = 1). In 3 cases, maternal antibody status was discovered because of the EFE diagnosis.Results.Endomyocardial hyperechogenicity predominated in the left atrium (n = 3) and mitral annulus (n = 3). No left-heart dysfunction was observed. Two mothers were treated with betamethasone. One mother chose to have a therapeutic abortion, and EFE was confirmed at autopsy. Electrocardiograms at birth (n = 4) did not show CHB. Other manifestations of NLES were present in all cases. One child had right ventricular hypoplasia and underwent a partial cavopulmonary anastomosis. At last followup (4–7 yrs), the other 3 children had normal heart function, and echocardiography showed a normal heart (n = 2) or mild persistent EFE (n = 1).Conclusion.Middle-term prognosis of isolated autoantibody-associated EFE may be better than previously reported, although the longterm prognosis remains unknown. We hypothesize that a fetal insult can lead to DCM.

To the Editor: We read with great interest the article by Rein et al1 that describes how fetal kinetocardiogram can accurately detect first-degree congenital heart block (CHB) in fetuses exposed to maternal anti-SSA/Ro and/or anti-SSB/La antibodies. We question, however, whether these cases of first-degree CHB were all necessarily pathological and consequently in need of treatment. The incidence of the first-degree CHB was 9% (6 affected fetuses among 70), which is much …