Systemic lupus erythematosus and pregnancy: Strategies before, during and after pregnancy to improve outcomes / Lupus eritematoso sistémico y embarazo: estrategias antes, durante y después del embarazo para mejorar los desenlaces

ABSTRACT Systemic lupus erythematosus is a multisystemic autoimmune disorder that predominantly affects women in reproductive years. Pregnancy in women with SLE is still considered a high-risk condition although several strategies may improve maternal and fetal outcomes. Preconception counseling is fundamental and should include identification of risk factors for adverse pregnancy outcomes, explanation of potential maternal and obstetric complications and timely planning of pregnancy. Risk stratification must consider end-organ damage, comorbidities, disease activity and autoantibodies profile in order to implement an individual-risk pregnancy monitoring plan by a multidisciplinary team. Hydroxychloroquine and low dose aspirin have shown to lower the risk of disease flares and preeclampsia with a good safety profile, so its use during pregnancy in all SLE patients is recommended. Lupus nephritis and preeclampsia share clinical and laboratory features hindering differentiation between both entities. Novel angiogenic markers and fetal ultrasound findings could be helpful in the differential diagnosis, especially after 20 weeks of gestation. Antiphospholipid antibodies, particularly lupus anticoagulant, are closely associated with obstetric complications. Therapy with low dose aspirin and heparin, according to risk profile, may improve live birth rates. Anti-Ro/La antibodies confer risk for neonatal lupus, and therefore preventive therapy and special fetal surveillance should be instituted.

RESUMEN El lupus eritematoso sistémico es un trastorno autoinmune multisistémico que afecta primordialmente a mujeres en edad reproductiva. El embarazo en mujeres con LES aún se considera una condición de alto riesgo, a pesar de que diversas estrategias pueden mejorar los desenlaces maternos y fetales. La asesoría preconcepción es fundamental, y debe incluir la identificación de factores de riesgo de desenlaces adversos del embarazo, una explicación de las posibles complicaciones maternas y obstétricas, así como la planificación oportuna del embarazo. La estratificación de riesgos debe considerar el daño orgánico terminal, las comorbilidades, la actividad de la enfermedad y el perfil de autoanticuerpos, a fin de llevar a cabo un plan de monitoreo de los riesgos individuales del embarazo por parte de un equipo multidisciplinario. La hidroxicloroquina y la aspirina a bajas dosis han demostrado reducir el riesgo de exacerbaciones de la enfermedad y de preeclampsia, con un buen perfil de seguridad, por lo cual se recomienda su uso en todas las pacientes con LES durante el embarazo. La nefritis lúpica y la preeclampsia comparten características clínicas y de laboratorio, obstaculizando la diferenciación entre las 2 entidades. Nuevos marcadores angiogénicos y hallazgos ecográficos fetales pudieran ser de utilidad para el diagnóstico diferencial, especialmente después de las 20 semanas de gestación. Los anticuerpos antifosfolípidos, en particular el anticoagulante lúpico, tiene una estrecha asociación con las complicaciones obstétricas. El tratamiento con aspirina a bajas dosis y heparina, según el perfil de riesgos, puede mejorar las tasas de nacimientos vivos. Los anticuerpos anti-Ro/La representan un riesgo de lupus neonatal, por lo cual debe instituirse tratamiento preventivo y vigilancia fetal especial.

Use of a screening questionnaire for systemic lupus erythematosus among pregnant women in a Mexican population.

OBJECTIVE: To conduct a diagnostic assessment of pregnant women using a screening questionnaire for SLE. MATERIALS AND METHODS: This was an analytical cross-sectional study carried out at the National Institute of Perinatology between 1 November 2019 and 28 February 2020, using a screening questionnaire for SLE. Antinuclear antibody and anti-double stranded DNA antibody tests and a clinical assessment by a rheumatologist were conducted for participants who obtained ≥4 positive responses on the questionnaire. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the screening questionnaire for SLE were calculated. RESULTS: The questionnaire survey was conducted with 540 pregnant patients, 22 of whom (4.1%) had ≥4 positive responses. An antinuclear antibody test was conducted in all aforementioned 22 patients; 17 (77.3%) showed titres of ≥1:80. Of the 22 patients, 19 (86.4%) underwent clinical assessment by a rheumatologist. The patients were classified according to the SLE classification criteria: 7/19 (36.9%) met the revised 1997 American College Rheumatology (ACR) criteria, 8/19 (42.1%) met the Systemic Lupus International Collaborating Clinics criteria and 7/19 (36.9%) met the 2019 ACR/EULAR criteria (sensitivity=0.86, specificity=0.97, PPV=0.77 and NPV=1 for antinuclear antibody titre of ≥1:80; sensitivity=0.88, specificity=0.98, PPV=0.37 and NPV=1 for SLE according to the 2019 ACR/EULAR criteria). CONCLUSIONS: The questionnaire showed high sensitivity and specificity in the diagnosis of SLE. Given its usability and cost:benefit ratio, this strategy should be used for all patients coming in for their first visit to determine who requires antinuclear antibody testing and who needs to be referred to a rheumatologist.

Physician's Experience and Disease Activity Affect the Impact of Ultrasound on the Treatment Decision in Rheumatoid Arthritis.

BACKGROUND/OBJECTIVE: The aim of this cross-sectional study was to explore which factors affect the impact of musculoskeletal ultrasound (MUS) on the treatment proposal among rheumatologists with different degree of experience. METHODS: Sixteen clinical vignettes summarized data from rheumatoid arthritis (RA) outpatients; vignettes included clinical evaluation and a blank section for a first treatment proposal; MUS information was then added, based on German Ultrasound score, followed by a blank section for treatment re-consideration, if applicable. During a 6 months period, each vignette was concomitantly presented to six trainees and six senior rheumatologists (SR); three SR had ≥15 years of experience. Participants were blinded to colleagues' responses. Appropriated statistics were used. RESULTS: Vignettes included data from female patients, who had a mean ± SD age of 43.3 ± 9 years, 7.6 ± 3.5 years of disease duration and comorbidities (68.8%). MUS induced treatment modification in 24% of evaluations, with similar percentage among SR and trainees. Within SR, more experienced rheumatologists (≥15 years) never translated MUS findings in a different treatment proposal, compared to 34% of those with lesser experience, p ≤ 0.0001. There were 60 clinical scenarios each, with remission and moderate disease activity, and 36 clinical scenarios each, with low and high disease activity. MUS-induced treatment modifications were more frequent in scenarios with low and moderate disease activity, compared to remission and high disease activity, p = 0.008. CONCLUSIONS: Physician's experience and disease activity level affect the impact of MUS on the treatment decision in RA outpatients. RA patients with intermediate disease activity may benefit from MUS incorporation to standard assessments.

Anti-RNP/Sm antibodies in patients with systemic lupus erythematosus and its role in thrombosis: a case-control study.

OBJECTIVE: To validate the association of thrombotic events with positive lupus anticoagulant (LA) and co-presence of anti-RNP/Sm, as well as the diagnostic accuracy of this combination of antibodies for thrombosis. METHODS: Case-control study of patients with systemic lupus erythematosus (SLE) who presented thrombosis after SLE diagnosis and controls with SLE without thrombosis. Comorbidities, traditional risk factors, clinical variables, and treatment were evaluated. Antiphospholipid (aPL) and anti-RNP/Sm antibodies were determined. RESULTS: Sixty-three cases and 63 controls were studied, 88% women, median age of 40 years, and disease duration of 135 months at study inclusion. No differences were found between groups regarding age, comorbidities, or clinical characteristics at SLE diagnosis. Patients with thrombosis were more frequently positive for anti-RNP/Sm (p = 0.001), IgG aCL (p = 0.02), IgG anti-B2GPI (p = 0.02), IgM anti-B2GPI (p = 0.02), LA (p < 0.001), the combination of anti-RNP/Sm + LA (p < 0.001), and aPL triple marker (p = 0.002), compared to controls. The combination of anti-RNP/Sm + LA, SLEDAI-2 K, and prednisone dose was associated with thrombosis (p < 0.05). The combination of anti-RNP/Sm + LA showed 56% sensitivity, 79% specificity, 73% positive predictive value, 64% negative predictive value, positive likelihood ratio (LR) 2.69, and negative LR 0.56 for predicting thrombosis. No difference was found in the comparison of area under the curve between LA alone and the combination of anti-RNP/Sm + LA (p = 0.73). CONCLUSION: Thrombosis was associated with disease activity, dose of prednisone, and the combination of anti-RNP/Sm antibodies and LA. This combination of antibodies could be useful in the identification of SLE patients at risk of thrombosis.