Soluble Flt-1, Placental Growth Factor, and Vascular Endothelial Growth Factor Serum Levels to Differentiate Between Active Lupus Nephritis During Pregnancy and Preeclampsia.

OBJECTIVE: To evaluate mean serum levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and soluble Flt-1 (sFlt-1) in pregnant patients with systemic lupus erythematosus (SLE) with inactive disease, active lupus nephritis, and preeclampsia for differential diagnosis between these conditions. METHODS: Pregnant women with SLE, with singleton pregnancies and no other autoimmune diseases, were classified according to disease activity (inactive SLE and active lupus nephritis) and the presence of preeclampsia. Serum samples were collected within 3 weeks of delivery and frozen for subsequent blinded analysis through the enzyme-linked immunosorbent assay method. RESULTS: A total of 71 women were included, with 41 classified as having inactive SLE (group 1; Systemic Lupus Erythematosus Pregnancy Disease Activity Index [SLEPDAI] score <4), 15 with a diagnosis of active lupus nephritis (group 2, SLEPDAI score ≥4, including renal criteria), and 15 with a diagnosis of preeclampsia (group 3). Patients in group 3 had higher mean levels of sFlt-1 and lower mean levels of PlGF compared to groups 1 and 2, both findings with statistical significance. The sFlt-1:PlGF ratio was also significantly higher in patients with preeclampsia, while mean VEGF levels were higher in pregnant woman with active lupus nephritis compared to patients with preeclampsia or inactive SLE. CONCLUSION: Evaluation of serum VEGF, PlGF, and sFlt-1 levels can differentiate between preeclampsia, inactive SLE, and active lupus nephritis during pregnancy.

Critical review of the current recommendations for the treatment of systemic inflammatory rheumatic diseases during pregnancy and lactation.

The crucial issue for a better pregnancy outcome in women with autoimmune rheumatic diseases is appropriate planning, with counseling of the ideal timing and treatment adaptation. Drugs used to treat rheumatic diseases may interfere with fertility or increase the risk of miscarriages and congenital abnormalities. MTX use post-conception is clearly linked to abortions as well as major birth defects, so it should be stopped 3months before conception. Leflunomide causes abnormalities in animals even in low doses. Although in humans, it does not seem to be as harmful as MTX, when pregnancy is detected in a patient on leflunomide, cholestyramine is given for washout. Sulfasalazine can be used safely and is an option for those patients who were on MTX or leflunomide. Azathioprine is generally the immunosuppressive of choice in many high-risk pregnancy centers because of the safety profile and its steroid-sparing property. Cyclosporine and tacrolimus can also be used as steroid-sparing agents, but experience is smaller. Although prednisone and prednisolone are inactivated in the placenta, we try to limit the dose to the minimal effective one, to prevent side effects. Antimalarials have been broadly studied and are safe during pregnancy and breastfeeding. Among biologic disease modifying anti-rheumatic agents (bDMARD), the anti-TNFs that have been used for longer are the ones with greater experience. The large monoclonal antibodies do not cross the placenta in the first trimester, and after conception, the decision to continue medication should be taken individually. The experience is larger in women with inflammatory bowel diseases, where anti-TNF is generally maintained at least until 30weeks to reduce fetal exposure. Live vaccines should not be administrated to the infant in the first 6months of life. Pregnancy data for rituximab, abatacept, anakinra, tocilizumab, ustekinumab, belimumab, and tofacitinib are limited and their use in pregnancy cannot currently be recommended.

Antiphospholipid Antibodies and Antiphospholipid Syndrome during Pregnancy: Diagnostic Concepts.

Antiphospholipid syndrome (APS) comprises of a wide spectrum of clinical and obstetric manifestations linked to the presence of antiphospholipid antibodies (aPL). APS was described in the context of lupus, and later as an isolated syndrome or primary APS. The presence of aPL, especially the lupus anticoagulant test, is associated with adverse pregnancy outcomes, such as fetal death, recurrent early miscarriages, pre-eclampsia, and placental insufficiency, but does not seem to influence infertility. High quality scientific data to support these associations, however, are lacking, and controversies arise about the definition of positive aPL (low vs medium-high titers) or even the definition of the adverse events. This review discusses APS classification criteria and the current debate about it.

Pregnancy morbidity in antiphospholipid syndrome: what is the impact of treatment?

Women with persistently circulating antiphospholipid antibodies (aPL) have a higher incidence of recurrent abortions, fetal losses, pre-eclampsia, and placental insufficiency. Current treatment of patients with antiphospholipid syndrome (APS) during pregnancy with heparin and aspirin can act by preventing clot formation and improving live birth rates, but other obstetric morbidities remain high, especially in patients with a history of thrombotic events. In addition to the classical thrombotic placental events, other factors involving inflammation and complement activation seem to play a role in certain complications. In this article, we will review how medications interfere in the pathogenic mechanisms of APS, discuss the impact of current recommended treatment on pregnancy morbidity, and analyze new promising therapies.

Pregnancy may aggravate arterial hypertension in women with Takayasu arteritis.

BACKGROUND: Takayasu arteritis (TA) is a rare chronic granulomatous inflammatory disease of the aorta and/or its major branches and more frequently affects female patients before menopause. Since persistent inflammation may lead to arterial ischemia, hypertension is an important complication of TA. OBJECTIVES: To evaluate gestational results and complications in patients with TA. METHODS: We conducted a retrospective analysis of the medical records of patients with TA admitted to the high risk pregnancy clinic for women with systemic autoimmune diseases at Hospital Universitário Pedro Ernesto. RESULTS: From 1998 to 2011 we followed 11 pregnancies in 9 patients with TA; the patients' age ranged from 17 to 42 years and disease duration from 2 to 28 years. In 7 of the 11 pregnancies, uncontrolled blood pressure occurred before labor and preeclampsia was diagnosed in one. Two deliveries were preterm, one newborn was treated for sepsis, and four (36%) had intrauterine growth restriction (IUGR). CONCLUSIONS: Close monitoring improves the perinatal outcomes in patients with TA who are more prone to develop hypertension, preeclampsia and IUGR. Disease activity was not observed in our group of patients during pregnancy. Coordinated care between the obstetric, rheumatologic and cardiologic teams is the ideal setting to follow pregnant women with TA.