Risk of adverse pregnancy outcomes prior to the onset of an autoimmune rheumatic disease: a systematic review

OBJECTIVES: An increased risk of adverse maternal and fetal pregnancy complications including pre-eclampsia, intrauterine growth restriction and small for gestational age, is well-described in women with autoimmune rheumatic disease (ARD) compared with the general population (GP). It is less clear however, whether this risk of adverse pregnancy outcome (APO) also exists in women with "preclinical ARD" (preARD) before they are diagnosed with an ARD many years post-partum. Therefore, we have undertaken a systematic review of available evidence on APO in patients who subsequently were diagnosed with a rheumatic disease to identify whether there is an increased risk in preARD. METHODS: The present study was reported in accordance with the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. A systematic literature review was performed using the online PubMed database. PreSLE and preRA patients were defined as those who, over the subsequent years, developed Systemic Lupus Erythematosus (SLE) or Rheumatoid Arthritis (RA) according to international classification criteria. RESULTS: A total of 176 articles were screened and 27 original articles selected for final analysis. PreRA was the most studied group with 15 studies of > 1600 pregnancies and preSLE was the second most studied preARD in pregnancy with 14 studies of > 1000 pregnancies. We found that patients who subsequently develop SLE have an increased burden of poor pregnancy outcomes compared with pregnant women from the GP but less APO compared with SLE pregnancies. In contrast, a similar rate of APO was found when preRA were compared with GP pregnancies. CONCLUSION: Our findings of an increased risk of APO in certain preARD highlights the relevance of an obstetric history during the first rheumatology appointment and the need for novel screening strategies to predict APO. Further research is required to elucidate the immune basis of adverse pregnancy outcomes in preclinical and clinical ARD

Thrombosis and Hyperinflammation in COVID-19 Acute Phase Are Related to Anti-Phosphatidylserine and Anti-Phosphatidylinositol Antibody Positivity

COVID-19; Antiphospholipid antibodies; ThrombosisCOVID-19; Anticuerpos antifosfolípidos; TrombosisCOVID-19; Anticossos antifosfolípids; TrombosiAntiphospholipid antibodies (APLA) are strongly associated with thrombosis seen in patients with antiphospholipid syndrome. In COVID-19, thrombosis has been observed as one of the main comorbidities. In patients hospitalised for COVID-19, we want to check whether APLA positivity is associated with COVID-19-related thrombosis, inflammation, severity of disease, or long COVID-19. We enrolled 92 hospitalised patients with COVID-19 between March and April 2020 who were tested for 18 different APLAs (IgG and IgM) with a single line-immunoassay test. A total of 30 healthy blood donors were used to set the cut-off for each APLA positivity. Of the 92 COVID-19 inpatients, 30 (32.61%; 95% CI [23.41–43.29]) tested positive for APLA, of whom 10 (33.3%; 95% CI [17.94–52.86]) had more than one APLA positivity. Anti-phosphatidylserine IgM positivity was described in 5.4% of inpatients (n = 5) and was associated with the occurrence of COVID-19-related thrombosis (p = 0.046). Anti-cardiolipin IgM positivity was the most prevalent among the inpatients (n = 12, 13.0%) and was associated with a recorded thrombosis in their clinical history (p = 0.044); however, its positivity was not associated with the occurrence of thrombosis during their hospitalisation for COVID-19. Anti-phosphatidylinositol IgM positivity, with a prevalence of 5.4% (n = 5), was associated with higher levels of interleukin (IL)-6 (p = 0.007) and ferritin (p = 0.034). Neither of these APLA positivities was a risk factor for COVID-19 severity or a predictive marker for long COVID-19. In conclusion, almost a third of COVID-19 inpatients tested positive for at least one APLA. Anti-phosphatidylserine positivity in IgM class was associated with thrombosis, and anti-phosphatidylinositol positivity in IgM class was associated with inflammation, as noticed by elevated levels of IL-6. Thus, testing for non-criteria APLA to assess the risk of clinical complications in hospitalised COVID-19 patients might be beneficial. However, they were not related to disease severity or long COVID-19.This research was funded by Synlab Group (Barcelona, Spain), Catedra UAB-Gravida de Medicina i Immunologia Reproductiva (Barcelona, Spain), and Sociedad Española de Medicina y Cirugía Cosmética (SEMCC, Barcelona, Spain)

Inflammatory immune-mediated adverse reactions induced by COVID-19 vaccines in previously injected patients with soft tissue fillers : A case series of 20 patients

Acord transformatiu CRUE-CSICBackground: Adverse events (AE) after COVID-19 vaccines, particularly, but not solely, with those messenger RNA (mRNA)-based vaccines, have rarely been reported in patients previously treated with dermal fillers (DF). Objective: To evaluate the morphology, clinical characteristics, the timing of presentation, and outcomes of inflammatory AE appeared in patients injected with DF, after anti-COVID-19 vaccination. Methods: Descriptive study of a case series of 20 consecutive patients collected after the occurrence of AE in previously filled areas post COVID-19 vaccination. Results: From January 2021 to July 2021, we analyzed 20 AE reactions triggered by COVID-19 vaccines in the previously mentioned cohort. They were vaccinated with Pfizer/Biontech (11; 55%), Moderna (5; 25%), Astra-Zeneca (3; 15%), and Sputnik (1; 5%). The most common manifestations were oedema/swelling, angioedema, erythema, skin induration, and granuloma. Less common reactions included myalgia and lymphadenopathy. In 13/20 (65%) cases, the AE appeared after the first dose of vaccine. These inflammatory AE appeared more rapidly after the second dose than after the first one. In 13/20 (65%) cases, the symptomatology subsided with anti-inflammatory/antihistaminic drugs, while spontaneously in 3/20 (15%). The manifestations are ongoing.in the remaining four cases (20%). Conclusion: Although probably rare, both RNA-based and adenovirus-based anti-COVID-19 vaccines can cause inflammatory bouts in patients previously treated with DF. In these cases, caution should be paid on subsequent vaccine doses, considering a tailored risk/benefit for any case before next vaccination

Predictive Model for Preeclampsia Combining sFlt-1, PlGF, NT-proBNP, and Uric Acid as Biomarkers

Angiogenic factors; Preeclampsia; Uric acidFactores angiogénicos; Preeclampsia; Ácido úricoFactors angiogènics; Preeclàmpsia; Àcid úricN-terminal pro-brain natriuretic peptide (NT-proBNP) and uric acid are elevated in pregnancies with preeclampsia (PE). Short-term prediction of PE using angiogenic factors has many false-positive results. Our objective was to validate a machine-learning model (MLM) to predict PE in patients with clinical suspicion, and evaluate if the model performed better than the sFlt-1/PlGF ratio alone. A multicentric cohort study of pregnancies with suspected PE between 24+0 and 36+6 weeks was used. The MLM included six predictors: gestational age, chronic hypertension, sFlt-1, PlGF, NT-proBNP, and uric acid. A total of 936 serum samples from 597 women were included. The PPV of the MLM for PE following 6 weeks was 83.1% (95% CI 78.5-88.2) compared to 72.8% (95% CI 67.4-78.4) for the sFlt-1/PlGF ratio. The specificity of the model was better; 94.9% vs. 91%, respectively. The AUC was significantly improved compared to the ratio alone [0.941 (95% CI 0.926-0.956) vs. 0.901 (95% CI 0.880-0.921), p < 0.05]. For prediction of preterm PE within 1 week, the AUC of the MLM was 0.954 (95% CI 0.937-0.968); significantly greater than the ratio alone [0.914 (95% CI 0.890-0.934), p < 0.01]. To conclude, an MLM combining the sFlt-1/PlGF ratio, NT-proBNP, and uric acid performs better to predict preterm PE compared to the sFlt-1/PlGF ratio alone, potentially increasing clinical precision.This work was supported by public funds obtained in competitive calls with peer review (grant PI19/00702), Insituto de Salud Carlos III, Spanish Ministry of Health, by the Maternal and Child Health and Development Network (SAMID, RD16/0022/0015), Instituto de Salud Carlos III, Madrid, Spain, the Spanish Clinical Research and Clinical Trials Platform, SCReN (Spanish Clinical Research Network), funded by the ISCIII-General Subdirectorate for Evaluation and Promotion of Research, through project PT13/0002/0028, integrated in the 2013–2016 R + D + I State Plan and co-financed by and the European Regional Development Fund (FEDER); and by the Primary Care Interventions to Prevent Maternal and Child Chronic Diseases of Perinatal and Developmental Origin Network (RICORS, RD21/0012/0001), Instituto de Salud Carlos III, Madrid, Spain, funded by the Recovery, Transformation and Resilience Plan 2017–2020, ISCIII, and by the European Union-Next Generation EU. Dr Cruz-Lemini is supported by Juan Rodés contract JR19/00047, Instituto de Salud Carlos III-Spanish Ministry of Health. Funding sources were not involved in study design, collection, analysis, and interpretation of data

Differences in Antiphospholipid Antibody Profile between Patients with Obstetric and Thrombotic Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is a systemic autoimmune condition characterised by the presence of antiphospholipid antibodies (aPL) associated with vascular thrombosis and/or pregnancy complications. In a cohort of 74 yet diagnosed APS individuals fulfilling Sydney laboratory criteria (twice positive for lupus anticoagulant, anticardiolipin, aCL, and/or anti-β2glycoprotein I, aβ2GPI), 33 out of 74 were obstetric APS (OAPS) and 41 thrombotic APS (TAPS) patients. 39% of TAPS patients were women. Although aPL detection was persistent, we observed an oscillatory aPL positivity in 56.7% and a transient seroconversion in 32.4% of APS patients at enrolment. Thus, we tested their sera in a line immunoassay that simultaneously detected IgG or IgM for criteria (aCL and aβ2GPI) and non-criteria (anti-phosphatidylserine, aPS; anti-phosphatidic acid, aPA; anti-phosphatidylinositol, aPI; anti-annexin 5, aA5; anti-prothrombin, aPT; anti-phosphatidylethanolamine; anti-phosphatidylglycerol, and anti-phosphatidylcholine) aPL. OAPS and TAPS patients displayed different but overlapping clusters based on their aPL reactivities. Specifically, while OAPS patients showed higher aPA, aPS, aA5, aβ2GPI and aPT IgM levels than TAPS patients, the latter displayed higher reactivity in aCL, aPI and aA5 IgG. Eventually, with a cut-off of the 99 th percentile established from a population of 79 healthy donors, TAPS patients significantly tested more positive for aCL and aA5 IgG than OAPS patients, who tested more positive for aPA, aPS and aβ2GPI IgM. Transiently seronegative APS patients showed non-criteria aPL positivity twice in sera obtained 3 months apart. Overall, our data show that APS patients presented clusters of aPL that define different profiles between OAPS and TAPS, and persistent non-criteria aPL positivity was observed in those who are transiently seronegativ