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.

[What's new in internal medicine?]. / Quoi de neuf en Médecine interne?

This article focuses on current trends in various autoimmune diseases of interest for the dermatologist. In the antiphospholipid syndrome, many news: better characterization of the severe disease, involvement of the mTOR pathway in the vasculopathy-induced renal disease, and diversification of the therapeutic approaches: use of mTOR inhibitors and several biologics, new various antiplatelet and anticoagulants. In dermatomyositis, new autoantibodies are better characterized with a good correlation with clinical disease; the results of a large study on genetic predisposition to the disease are available. There are also some therapeutic innovations in systemic sclerosis: benefit of rituximab that seems well tolerated, the results of a large controlled European study about aggressive immunoablative chemotherapy followed by autologous stem cells have just been published, intralesional stem cells injections in the fingers of sclerodactylic patients. Finally, news in celiac disease that is constantly increasing and whose mild forms often have cutaneous manifestations, leading to diagnosis.

[Which workup should be performed after a pregnancy complicated with vasculo-placental disorder?] / Quel bilan proposer après une grossesse compliquée de pathologie vasculo-placentaire ?

Vasculo-placental disorders include pregnancy complications resulting from placental dysfunction of vascular origin, i.e. pre-eclampsia, HELLP syndrome, intrauterine growth retardation (IUGR), placental abruption and stillbirth of vascular origin. Pre-eclampsia should be investigated for antiphospholipid syndrome (APS) in case of severe pre-eclampsia and premature delivery before 34 weeks of gestation. In addition to testing for APS, pathological report of the placenta can identify some anatomical predispositions to placental vascular malperfusion, as well as chronic placental inflammatory lesions and excess fibrin deposits. The latter two are associated with IUGR and recurrent stillbirth, reflecting a dysimmune process of maternal origin. The internal medicine and obstetrics consultation, organized two months after delivery, combines the postnatal visit with an assessment of the causes of vasculo-placental disorders, and enables to inform patients about the management of future pregnancies and their cardiovascular health.

Acute Q fever revealed by an anti-phospholipid syndrome: A case report.

INTRODUCTION: Q fever is a zoonosis caused by Coxiella burnetii. Acute infection is mainly asymptomatic. In other cases it mainly causes a flu-like illness, a pneumonia, or an hepatitis. We present an atypical case of an acute Q fever revealed by a massive pleural effusion. CASE REPORT: We report the case of a 43-year-old man referred to our hospital for an acute respiratory distress. Further analyses showed an exudative eosinophilic pleural effusion, associated with a pulmonary embolism and a deep femoral vein thrombosis. Aetiologic explorations revealed an acute Q fever (IgM and IgG against C. burnetii phase II antigens) associated with anti-phospholipids. The outcome was favorable with vitamin K antagonists, doxycycline, and hydroxychloroquine, till the negativation of the anti-phospholipid antibodies. DISCUSSION AND CONCLUSION: During acute C. burnetii infections, anti-phospholipid antibodies are highly prevalent but thrombotic complications are rare. The 2023 ACR/EULAR APS criteria restricts the diagnosis of APS, as in our case of acute severe infection. In front of an atypical pneumonia and/or thrombotic events, screening of C. burnetii and anti-phospholipid antibodies could be useful. Given its low level of evidence, prolongated treatment by doxycycline, hydroxychloroquine ± anticoagulant for C. burnetii's associated anti-phospholipid syndrome is discussed, but succeeded in our case.

[Libman-Sachs endocarditis and ischemic stroke : A case report]. / Endocardite de Libman-Sachs et accident vasculaire cérébral ischémique : à propos d'un cas.

Libman-Sacks endocarditis is a rare cardiac manifestation of anti-phospholipid syndromes, in which non-infectious thrombotic vegetations are found on the heart valves. Most patients are asymptomatic whereas the risk of thromboembolism is considerable. Diagnostic work-up is based on questioning and clinical examination data looking for extracardiac signs, biological data and also on imaging, and, above all, echocardiography. We report the case of a 47-year-old female patient with no known history who is admitted to hospital with paresthesia of the right hemi-body associated with dysarthria. Cerebral CT scan confirms a paraventricular ischemic stroke. The etiological work-up for stroke is negative except the transesophageal echocardiogram which reveals mitral valve vegetations. Further investigations lead to the diagnosis of Libman-Sacks endocarditis. Treatment with Coumadin is started, with a target INR of between 2 and 3, as recommended. The clinical course was favourable, with stable lesions on transoesophageal echocardiography carried out later.

French National Diagnostic and Care Protocol for antiphospholipid syndrome in adults and children.

Antiphospholipid syndrome (APS) is a chronic autoimmune disease involving vascular thrombosis and/or obstetric morbidity and persistent antibodies to phospholipids or certain phospholipid-associated proteins. It is a rare condition in adults and even rarer in children. The diagnosis of APS can be facilitated by the use of classification criteria based on a combination of clinical and biological features. APS may be rapidly progressive with multiple, often synchronous thromboses, resulting in life-threatening multiple organ failure. This form is known as "catastrophic antiphospholipid syndrome" (CAPS). It may be primary or associated with systemic lupus erythematosus (associated APS) and in very rare cases with other systemic autoimmune diseases. General practitioners and paediatricians may encounter APS in patients with one or more vascular thromboses. Because APS is so rare and difficult to diagnosis (risk of overdiagnosis) any suspected case should be confirmed rapidly and sometimes urgently by an APS specialist. First-line treatment of thrombotic events in APS includes heparin followed by long-term anticoagulation with a VKA, usually warfarin. Except in the specific case of stroke, anticoagulants should be started as early as possible. Any temporary discontinuation of anticoagulants is associated with a high risk of thrombosis in APS. A reference/competence centre specialised in autoimmune diseases must be urgently consulted for the therapeutic management of CAPS.

[Prevalence and etiological profiles of atypical localization venous thrombosis : A descriptive multicenter study]. / Prévalence et profils étiologiques des thromboses veineuses de localisation atypique : une étude multicentrique descriptive.

INTRODUCTION: Venous thrombosis of unusual sites is much rarer than in the lower limbs and requires a rigorous etiological approach. The objective was to describe the clinical and progressive peculiarities of unusual localization venous thrombosis as well as their etiologies. PATIENTS AND METHODS: Multicenter descriptive retrospective study of hospitalized patient records in the two large Hospital Centers, Antananarivo, Madagascar between 2017 and 2020 in which the diagnosis of unusual venous thrombosis was confirmed by imaging. RESULTS: Seventy-seven thrombosis of atypical localization were present in fifty-nine patients identified. These were 24 men and 35 women with an M/F sex ratio of 0.68. The mean age of our patients was 49.4 years (± 16.76). Thrombosis seated in the majority of cases in the portal veins (n ​​= 27), cerebral veins (n ​​= 20), vena cava (n = 10), splenic veins (n ​​= 5), upper limbs and splenomearic trunk (each n = 4), Renal vein (n = 3). Venous thrombosis had occurred following tobacco intoxication (n = 15 cases); bed rest (n = 10); surgical intervention (n = 4). The aetiological assessment revealed a neoplastic origin in 27 cases (45.77%) dominated by hepatocellular carcinoma (n = 13). the antiphospholipid antibody syndrome dominates the case of autoimmune causes (n = 4). In terms of mortality, there were no deaths during the initial hospitalization. Eight patients had died, 4 of them due to hepatocellular carcinoma, 2 after surgery, and 1 each due to kidney cancer and liver cirrhosis. The mean follow-up period was 34.03 ± 51.5 days. CONCLUSION: Unusual thrombosis, although rare, constitute a real challenge in the etiological approach. In clinical practice, the description of these thrombosis would allow us to understand their pathophysiological mechanism in order to plan the best management.

[Contribution of antiphosphatidylserine/prothrombin (anti-PS/PT) antibody detection in the diagnosis and management of antiphospholipid syndrome (APS)]. / Apport de la détection des anticorps antiphosphatidylsérine/prothrombine (aPS/PT) dans le diagnostic et la prise en charge du syndrome des antiphospholipides (SAPL).

Antiphospholipid syndrome (APS) is an autoimmune disease and one of the most common causes of acquired thrombophilia. It is characterised by the occurrence of thrombotic or obstetric events associated with the presence of persistent antiphospholipid antibodies. The diagnosis can be challenging, particularly because some biological tests can be disturbed by anticoagulant treatment or inflammation. In the recent years, new antiphospholipid antibodies, including anti-phosphatidylserine/prothrombin antibodies (anti-PS/PT), have emerged but their clinical significance and causality remain uncertain. Biologically, several studies have found a strong correlation between the presence of lupus anticoagulant (LA) and anti-PS/PT antibodies. Clinically, the presence of anti-PS/PT antibodies is associated with an increased risk of thrombosis and obstetric complications. There is also an association with thrombocytopenia, suggesting that the presence of anti-PS/PT antibodies may be associated with more severe clinical APS. Among seronegative APS patients, 6-17% of patients are positive for anti-PS/PT antibodies. This might influence the therapeutic management of patients. This article aims to provide an update on contribution of anti-PS/PT antibodies detection for the diagnosis and management of APS.

[Heart involvement in systemic lupus erythematosus and antiphospholipid syndrome]. / Cœur et médecine interne : lupus systémique et syndrome des antiphospholipides.

Cardiac involvement in systemic lupus (SL) and antiphospholipid syndrome (APS) can be due to variables and involve different presentations. Pericarditis is the most common lupus manifestation and occurs in 16% to 25% of patients. While corticosteroids are usually very effective, colchicine may avoid steroids and prevent relapse. Myocarditis during SL is rare and often inaugural. They may manifest as chest pain, acute heart failure, arrhythmias or conduction disturbances, and may progress to dilated cardiomyopathy and/or permanent heart failure. Their prognosis is however generally good, even in the absence of treatment with cyclophosphamide for the less serious forms. Finally, coronary involvement in SL is most often due to atherosclerotic, thrombotic origin (generally in the context of associated APS), and exceptionally explained by coronary vasculitis. During APS, valve disease is frequent and usually asymptomatic. Thrombotic damage can be (1) coronary, typically manifesting as a myocardial infarction in a young subject with healthy coronary arteries, (2) much more rarely intracardiac, or (3) microcirculatory, generally as part of a catastrophic antiphospholipid syndrome (CAPS) leading to a multiorgan failure. Finally, iatrogenic cardiac manifestations can exceptionally be seen during treatment with cyclophosphamide or antimalarials characterized by conduction disorders and/or heart failure.

[Libman-Sacks endocarditis under apixaban in a patient with a high-risk profile venous antiphospholipid syndrome]. / Une endocardite de Libman-Sacks survenant sous apixaban chez une patiente atteinte de SAPL veineux de profil à haut risque.

INTRODUCTION: Libman-Sacks endocarditis is a rare complication of antiphospholipid syndrome. Anti-vitamin K therapy is the standard treatment, although valvular replacement surgery may be required in some severe cases. In the latest EULAR recommendations, it is advised not to use direct oral anticoagulants in the management of antiphospholipid syndrome, especially of high-risk profile. CASE REPORT: We present a case of a mitral Libman-Sacks endocarditis complicated with multiple strokes occurring in the setting of an antiphospholipid syndrome with triple positive antibody profile in a 63-year-old woman with multiple sclerosis. She was previously treated with apixaban for two years. Tinzaparin followed by prolonged warfarine treatment and two months of hydroxychloroquine resulted in valvular improvement. CONCLUSION: To our knowledge, this is the first case of Libman-Sacks endocarditis occurring during apixaban therapy in a patient with antiphospholipid syndrome. This severe case highlights the inefficiency of direct oral anticoagulants to prevent thrombotic events in the antiphospholipid syndrome.

[Seronegative antiphospholipid syndrome: Myth or reality?] / Syndrome des antiphospholipides « séronégatif ¼ : mythe ou réalité ?

The antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and/or obstetrical manifestations and the persistent presence, at least 12 weeks apart, of antiphospholipid antibodies (aPL) such as lupus anticoagulant (LA) and/or anticardiolipin antibodies (ACL) and/or anti-ß2 glycoprotein I antibodies (aß2GPI). The finding of patients with clinical profile highly suggestive of APS but who are negative for conventional biological criteria has led to the concept of seronegative APS. In the last few years, new antigen targets and methodological approaches have been employed to more clearly identify this syndrome in patients with thrombosis or obstetrical complications without conventional aPL. Although seronegative APS is still controversial, there is increasing recognition of the existence of this subgroup. However, clinical relevance of non conventional aPL need to be confirmed by efforts toward standardizing new biological tools and longitudinal studies involving large cohort of patients.

[Bilateral adrenal hemorrhage under apixaban in primary antiphospholipid syndrome]. / Nécrose hémorragique bilatérale des surrénales sous apixaban : penser au syndrome des antiphospholipides ?

INTRODUCTION: Adrenal hemorrhage is a classical but rare complication of antiphospholipid syndrome, revealing diagnosis in one third of the cases. Anti-vitamin K therapy is the standard treatment but direct oral anticoagulants are discussed as an alternative. In the latest recommendations, it is advised not to use direct oral anticoagulants in the setting of antiphospholipid syndrome. CASE REPORT: We present a case of bilateral adrenal hemorrhage revealing primary antiphospholipid syndrome with triple positive antibody profile, in a 47-year-old man treated by apixaban for previous venous thromboembolism. CONCLUSION: To our knowledge, it is the first case of adrenal hemorrhage occurring during apixaban treatment in a patient with antiphospholipid syndrome. This case illustrates the inefficacy of direct oral anticoagulants to prevent thrombotic events in antiphospholipid syndrome, in accordance with the latest recommendations.

[Which place of antiphosphatidylethanolamine antibodies research in seronegative antiphospholipid syndrome suspicion?] / Quelle place pour la recherche des anticorps antiphosphatidyléthanolamine dans la suspicion du syndrome des antiphospholipides séronégatif ?

PURPOSE: Antiphospholipid syndrome (APS) is a clinico-biological syndrome, which associates vascular injury and persisting antiphospholipid antibodies (aPL). Patients with clinical symptoms of APS but without aPL are defined as "seronegative APS" (SNAPS). The aim of this study was to evaluate antiphosphatidylethanolamine antibody (aPE) investigation in patients with SNAPS suspicion. METHODS: This retrospective study was conducted in patients with SNAPS suspicion. A homemade enzyme-linked immunosorbent assay (ELISA) was used to search for aPE. The results of this homemade method were compared with those from a global screening ELISA. RESULTS: Two hundred twenty-eight patients with SNAPS suspicion were included. Among them, 58.3% had a thrombotic event. The homemade ELISA found positive persisting aPE in 23 patients (10%): 15 with a thrombotic event, 6 with obstetrical morbidity and 2 with a combined event. The global screening ELISA was positive in only 11 of these 23 patients (47.8%). CONCLUSION: These results suggest the implication of aPE in SNAPS.

[Laboratory diagnosis of antiphospholipid syndrome: From criteria to practice]. / Diagnostic biologique du syndrome des antiphospholipides : des critères à la pratique.

The antiphospholipid syndrome is a bioclinical entity defined by thrombosis and/or obstetrical complications in the presence, at least 12 weeks apart, of antiphospholipid antibodies detected by coagulation test (lupus anticoagulant) or immunological assays (anticardiolipin, anti-ß2-glycoprotein I antibodies). Biological markers' improvement such as anti-phosphatidylserine/prothrombin and biological score should allow better patients' management and preventive therapeutic for thrombosis and obstetrical complications. This review describes different types of antibodies, link between biological profile and risk level of thrombosis events/obstetrical complications and gives practical advice to interpret biological results.

[For a targeted use of aspirin]. / Pour une prescription ciblée de l'aspirine.

The use of low-dose aspirin in pregnancy should remain a highly targeted indication since its long-term safety has not been established and should be restricted to women at high risk of vascular complications. Indications for which the benefit of aspirin has been shown are women with a history of preeclampsia responsible for a premature birth before 34 weeks, those having at least two history of preeclampsia, those with an antiphospholipid syndrome and those with lupus associated with positive antiphospholipid antibodies or renal failure. In all other cases, the level of evidence of the benefit of aspirin is insufficient to recommend its routine prescription.

Lupus anticoagulant-hypoprothrombinemia syndrome presenting with co-existing cerebral venous thrombosis and subdural hemorrhage.

The lupus anticoagulant-hypoprothrombinemia syndrome (LA-HPS) - the association of acquired factor II deficiency and lupus anticoagulant - is a rare disease that may cause a predisposition not only to thrombosis but also to severe bleeding. We are reporting on a 36-year-old female patient presenting with co-existing cerebral venous thrombosis and subdural hemorrhage. The coagulation screening showed a prolonged prothrombin time (PT), activated partial thromboplastin time (aPTT), and a normal fibrinogen level and platelet count. Evaluation of the clotting factors revealed decreased levels of factors II (37%). Factors V, VIII, IX and XI were normal. Lupus anticoagulant (LA) was demonstrated by the Dilute Russell's Viper Venom Test (DRVVT). Immunological work-up was positive for IgG type anticardiolipines antibodies (aCL). Successful management consisted first of oral prednisone (60mg/d). Thus, anticoagulation was introduced once factor II had stabilized.

[Acute anterior myocardial infarction as presenting feature of antiphospholipid syndrome related lupus arthritis]. / Infarctus du myocarde antérieur inaugural révélateur d'un syndrome des antiphospholipides dans le cadre d'une polyarthrite lupique.

INTRODUCTION: Antiphospholipid syndrome is an autoimmune disorder causing venous and arterial thrombosis. Acute coronary complications are rare but potentially dramatic. CASE REPORT: We report a 39-year-old woman who presented with an acute anterior myocardial infarction after intravenous corticosteroids as part of the treatment of lupus arthritis and revealing antiphospholipid syndrome. Emergency coronary angiography was performed with drug-eluting stent angioplasty despite the need for anticoagulation and dual antiplatelet therapy. CONCLUSION: Antiplatelet and anticoagulant therapy management is pivotal in patients with antiphospholipid syndrome and acute coronary syndrome to prevent thrombosis recurrence.

[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.