Bleeding complications and antithrombotic treatment in 264 pregnancies in antiphospholipid syndrome.

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.

Pregnancy and contraception in systemic and cutaneous lupus erythematosus.

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.

[Prevention of infections in adults and adolescents with systemic lupus erythematosus: Guidelines for the clinical practice based on the literature and expert opinion]. / Prévention des infections au cours du lupus systémique chez l'adulte et l'adolescent : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

PURPOSE: To develop French recommendations about the management of vaccinations, the screening of cervical cancer and the prevention of pneumocystis pneumonia in systemic lupus erythematosus (SLE). METHODS: Thirty-seven experts qualified in internal medicine, rheumatology, dermatology, nephrology and pediatrics have selected recommendations from a list of proposition based on available data from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Inactivated vaccines do not cause significant harm in SLE patients. Experts recommend that lupus patient should receive vaccinations accordingly to the recommendations and the schedules for the general public. Pneumococcal vaccination is recommended for all SLE patients. Influenza vaccination is recommended for immunosuppressed SLE patients. Live attenuated vaccines should be avoided in immunosuppressed patients. Yet, recent works suggest that they can be considered in mildly immunosuppressed patients. Experts have recommended a cervical cytology every year for immunosuppressed patients. No consensus was obtained for the prevention of pneumocystis pneumonia. CONCLUSION: These recommendations can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

[Liver diseases and pregnancy]. / Pathologies hépatiques et grossesse.

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.

[Systemic lupus erythematosus and antiphospholipid syndrome: How to manage pregnancy?]. / Lupus systémique et syndrome des antiphospholipides : comment prendre en charge la grossesse ?

Pregnancy 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: Literature review]. / « Lupus néonatal ¼ : revue de la littérature.

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.

[In vitro fertilization and systemic lupus erythematosus or antiphospholipid syndrome: An update]. / Fécondation in vitro au cours du lupus érythémateux systémique ou du syndrome des antiphospholipides : mise au point.

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 pre-pregnancy counseling]. / La consultation préconceptionnelle.

Pre-pregnancy counseling is one of the keys of success of pregnancy in women with autoimmune or systemic diseases, especially lupus or antiphospholipid syndrome. This type of consultation should be offered to all women with systemic diseases, giving the possibility to allow a pregnancy or to explain why this project should be delayed, to anticipate some problems, to give comprehensive informations to the couple, to organize the multidisciplinary monitoring, to adapt treatments, and finally, to verify the validity of some vaccinations. The generalization of pre-pregnancy counseling should allow to minimize risks for both mother and fetus, then, to improve the prognosis of these high risk pregnancies.

[Screening and management of cardiovascular risk factors in systemic lupus erythematosus: Recommendations for clinical practice based on the literature and expert opinion]. / Dépistage et prise en charge du risque cardiovasculaire au cours du lupus systémique : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

PURPOSE: To develop French recommendations about screening and management of cardiovascular risk factors in systemic lupus erythematosus (SLE). METHODS: Thirty-nine experts qualified in internal medicine, rheumatology and nephrology have selected recommendations from a list developed based on evidence from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Experts recommended an annual screening of cardiovascular risk factors in SLE. Statins should be prescribed for primary prevention in SLE patients based on the level of LDL-cholesterol and the number of cardiovascular risk factors, considering SLE as an additional risk factor. For secondary prevention, experts have agreed on an LDL-cholesterol target of <0.7 g/L. Hypertension should be managed according to the 2013 European guidelines, using renin-angiotensin system blockers as first line agents in case of renal involvement. Aspirin can be prescribed in patients with high cardiovascular risk or with antiphospholipid antibodies. CONCLUSION: These recommendations about the screening and management of cardiovascular risk factors in SLE can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

[Chronic maternal diseases and pregnancy losses. French guidelines]. / Pathologies maternelles chroniques et pertes de grossesse. Recommandations françaises.

AIM: To review the available data on maternal chronic diseases and pregnancy losses. MATERIAL AND METHODS: We searched PubMed and the Cochrane library with pregnancy loss, stillbirth, intrauterine fetal demise, intrauterine fetal death, miscarriage and each maternal diseases of this paper. RESULTS: Antiphospholipid antibodies (anticardiolipin, anti-beta-2-glycoprotein, lupus anticoagulant) should be measured in case of miscarriage after 10WG confirmed by ultrasound (grade B) and an antiphospholipid syndrome should be treated by a combination of aspirin and low-molecular-weight heparin during a subsequent pregnancy (grade A). We do not recommend testing for genetic thrombophilia in case of first trimester miscarriage (grade B) or stillbirth (grade C). Glycemic control should be a goal before pregnancy for women with pregestational diabetes to limit the risks of pregnancy loss (grade A) with a goal of prepregnancy HbA1c<7%. Overt and subclinical hypothyroidisms should be treated by L-thyroxin during pregnancy to reduce the risks of pregnancy loss (grade A). Women who are positive for TPOAb should have TSH concentrations follow-up during pregnancy and subsequently treated by L-thyroxin if they develop subclinical hypothyroidism (grade B). CONCLUSIONS: Prepregnancy management of most chronic maternal diseases, ideally through prepregnancy multidisciplinary counseling, reduces the risks of pregnancy loss.

[The myeloproliferative neoplasms-related glomerulopathy]. / Les glomérulopathies associées aux néoplasies myéloprolifératives.

PURPOSE: Myeloproliferative neoplasms (MPN) are hematological disorders characterized by clonal expansion of one or more medullary lines. Renal complications are rare, chiefly as acute renal failure. Glomerular involvement is exceptional METHODS: We report on a retrospective multicenter case series of eight patients who presented with a glomerulopathy (GP) associated with MPN RESULTS: All GP were revealed by a major proteinuria frequently associated with nephrotic syndrome and oedema. Histology was mainly characterized by lesions of focal segmental glomerulosclerosis associated with increased mesangial cellularity. The pathophysiology is still unclear but platelet-derived growth factor (PDGF) and transforming growth factor-ß (TGF-ß), which play a central role in the MPN may be involved. A majority of patients developed chronic renal failure despite of a therapy intended to block the renin-angiotensin system CONCLUSION: Monitoring of proteinuria during the follow-up of MPN would allow earlier diagnosis of renal involvement. Further studies on a larger scale are needed to specify the pathophysiological mechanisms involved and the management of these complications.

[Preauricular lymphadenopathy related to Bartonella henselae]. / Adénopathies prétragiennes liées à Bartonella henselae.

INTRODUCTION: Cat scratch disease is characterized by adenitis with usually positive outcome. We reported two cases of cat scratch disease with preauricular involvement occurring in immunocompetent patients. OBSERVATIONS: Observation 1: a 28-year-old man had a recent onset of left cervical swelling, with a peripheral facial paralysis and liver cytolysis. Serologies for EBV, viral hepatitis, CMV, HIV and toxoplasma were negative. Node excision biopsy suggested granulomatous lymphadenitis and Bartonella henselae PCR on lymph node was positive. With doxycyclin for 3 months, associated with rifampicin for 15 days, abnormal liver function disappeared and facial paralysis improved. Observation 2: a 17-year-old man had parotid swelling associated with right posterior cervical lymphadenopathies associated with fever and profuse sweating. A large right preauricular lymphadenopathy with necrotic remodeling was visible on the CT-scan. Lymph fluid B. henselae PCR was positive. Positive outcome occurs after surgical drainage and short azithromycin treatment. CONCLUSION: Physicians should be aware of the rare preauricular localization of cat scratch disease and ask for contact with a cat. Parotid tumor localization, lymphoma or tuberculosis should be ruled out. Diagnosis is based on the B. henselae PCR. Outcome is often spontaneously positive but surgical treatment may be required.

[Recurrent pericarditis related to primary pericardial malignant mesothelioma]. / Péricardite récidivante : traquer le mésotheliome péricardique primitif.

INTRODUCTION: Most of recurrent pericarditis are idiopathic and only 15 to 20% have a specific diagnosis. Primary pericardial mesothelioma is a rare cause of recurrent pericarditis. Diagnosis can be challenging and antedates patient's death in only 10 to 20% of cases. Histology of mesothelioma and immunohistochemistry are mandatory for the diagnosis. Median of survival before using pemetrexed was about 6 months after diagnosis. CASE REPORT: We report the history of a 64-year-old woman for which repeated biopsy for recurrent pericarditis was necessary to diagnose a primary pericardial mesothelioma. The first biopsy had only found mesothelial hyperplasia. CONCLUSION: This case report highlights the necessity of repeat pericardial biopsy in the case of adverse outcome.

Is IgG4-Related Disease a Cause of Xerostomia? A Cohort Study of 60 Patients.

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.

[Mesenteric panniculitis]. / Panniculite mésentérique.

Mesenteric panniculitis is a nonspecific inflammatory process affecting the fatty tissue at the root of the mesentery. This term is also used to describe the clinical and imaging findings in this disorder. Mesenteric panniculitis can be a misleading term: it is commonly misused to design an increased density of the mesentery without prejudice regarding the etiology. Pain is the main clinical symptom. Half of the patients are asymptomatic. There is a palpable mass in half of cases. Laboratory tests sometimes reveal an acute phase reaction of varying intensity. Mesenteric panniculitis is suspected when CT scan shows increased density of the mesenteric fat. Nevertheless, only histological examination could establish the diagnosis. Histologic examination may reveal various stages: lipodystrophy (the first stage when fat necrosis is predominant), mesenteric panniculitis (a majority of infiltrating lymphocytes), sclerosing mesenteritis (the end stage when fibrosis is predominant). Histopathologic differential diagnoses are lymphomas, lipomas, liposarcomas that can mimic mesenteric panniculitis on CT scan. Mesenteric panniculitis is associated with various diseases, especially with intra-abdominal inflammatory process. It also can be idiopathic. Rare complications can occur with vascular or digestive tract compressions. Empirical treatment is only useful in symptomatic patients. Colchicine, corticosteroids or immunosuppressive agents can be used. The only interest of surgery is the histological confirmation of the diagnosis. A better understanding of the pathophysiology of the immunoregulatory functions of adipose tissue will improve mesenteric panniculitis management.

[Pregnancy and antiphospholipid syndrome]. / Grossesse et syndrome des antiphospholipides.

Antiphospholipid syndrome (APS) is associated with a risk of obstetrical complications, affecting both the mother and the fetus. Obstetrical APS is defined by a history of three consecutive spontaneous miscarriages before 10 weeks of gestation (WG), an intra-uterine fetal death after 10 WG, or a premature birth before 34 WG because of severe pre-eclampsia, eclampsia or placental adverse outcomes (intrauterine growth retardation, oligohydramnios). Pregnancy in women with a diagnosis of obstetric APS is at increased risk for placental abruption, HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome and thrombosis that may be part of a catastrophic antiphospholipid syndrome (CAPS). A previous thrombosis and the presence of a lupus anticoagulant are risk factors for pregnancy failure. A multidisciplinary approach, associating the internist, the anesthesiologist and the obstetrician, is recommended for these high-risk pregnancies. Preconception counseling is proposed to identify pregnancy contraindications, and to define and adapt the treatment prior and during the upcoming pregnancy. Heparin and low-dose aspirin are the main treatments. The choice between therapeutic or prophylactic doses of heparin will depend on the patient's medical history. The anticoagulant therapeutic window for delivery should be as narrow as possible and adapted to maternal thrombotic risk. There is a persistent maternal risk in the postpartum period (thrombosis, HELLP syndrome, CAPS) justifying an antithrombotic coverage during this period. We suggest a monthly clinical and biological monitoring which can be more frequent towards the end of pregnancy. The persistence of notches at the Doppler-ultrasound evaluation seems to be the best predictor for a higher risk of placental vascular complications. Treatment optimization and multidisciplinary antenatal care improve the prognosis of pregnancies in women with obstetric APS, leading to a favorable outcome most of the time.