-
Annals of the Rheumatic Diseases May 2024To analyse the new evidence (2018-2022) for the management of systemic lupus erythematosus (SLE) to inform the 2023 update of the European League Against Rheumatism...
OBJECTIVES
To analyse the new evidence (2018-2022) for the management of systemic lupus erythematosus (SLE) to inform the 2023 update of the European League Against Rheumatism (EULAR) recommendations.
METHODS
Systematic literature reviews were performed in the Medline and the Cochrane Library databases capturing publications from 1 January 2018 through 31 December 2022, according to the EULAR standardised operating procedures. The research questions focused on five different domains, namely the benefit/harm of SLE treatments, the benefits from the attainment of remission/low disease activity, the risk/benefit from treatment tapering/withdrawal, the management of SLE with antiphospholipid syndrome and the safety of immunisations against varicella zoster virus and SARS-CoV2 infection. A Population, Intervention, Comparison and Outcome framework was used to develop search strings for each research topic.
RESULTS
We identified 439 relevant articles, the majority being observational studies of low or moderate quality. High-quality randomised controlled trials (RCTs) documented the efficacy of the type 1 interferon receptor inhibitor, anifrolumab, in non-renal SLE, and belimumab and voclosporin, a novel calcineurin inhibitor, in lupus nephritis (LN), when compared with standard of care. For the treatment of specific organ manifestations outside LN, a lack of high-quality data was documented. Multiple observational studies confirmed the beneficial effects of attaining clinical remission or low disease activity, reducing the risk for multiple adverse outcomes. Two randomised trials with some concerns regarding risk of bias found higher rates of relapse in patients who discontinued glucocorticoids (GC) or immunosuppressants in SLE and LN, respectively, yet observational cohort studies suggest that treatment withdrawal might be feasible in a subset of patients.
CONCLUSION
Anifrolumab and belimumab achieve better disease control than standard of care in extrarenal SLE, while combination therapies with belimumab and voclosporin attained higher response rates in high-quality RCTs in LN. Remission and low disease activity are associated with favourable long-term outcomes. In patients achieving these targets, GC and immunosuppressive therapy may gradually be tapered. Cite Now.
PubMed: 38777375
DOI: 10.1136/ard-2023-225319 -
Annals of Medicine and Surgery (2012) May 2024The optimal treatment regimen for patients with Hughes syndrome remains unclear. Therefore, the authors sought to compare the outcomes of warfarin vs. factor Xa... (Review)
Review
BACKGROUND
The optimal treatment regimen for patients with Hughes syndrome remains unclear. Therefore, the authors sought to compare the outcomes of warfarin vs. factor Xa inhibitors in patients with Hughes syndrome.
METHODS
MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) comparing 8 efficacy and safety of warfarin and factor Xa inhibitors in patients with Hughes syndrome. Recurrent thrombosis, all-cause mortality, stroke, adverse reactions, and bleeding were among 10 outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate 11 relative risks (RRs) with 95% CIs.
RESULTS
The analysis included 625 patients from four RCTs and one post-hoc analysis. Meta-analysis showed a statistically non-significant difference between factor Xa inhibitors and warfarin in the recurrent thrombosis risk (arterial or venous) [RR 2.77 (95%, CI 0.79, 9.65); =0.11, I=50%]. Consistent results were revealed among patients with a previous history of arterial thrombosis [RR 2.76 (95% CI 0.93, 8.16); =0.75, I=0%], venous thrombosis [RR 1.71 (95% CI 0.60, 4.84); =0.31, I=15%] and patients who were triple antiphospholipid antibodies (aPL) positive [RR 4.12 (95% CI 0.46, 37.10); 21 =0.21, I=58%]. Factor Xa inhibitors were significantly associated with an increased risk of stroke [RR 8.51 (95% CI 2.35, 13.82); =0.47, I=0%].
CONCLUSION
Factor Xa inhibitors exhibited an increased risk of stroke among patients with Hughes syndrome. In addition, although not significant, the higher RRs among patients on factor Xa inhibitors may indicate a higher risk of thrombotic events associated with factor Xa inhibitors.
PubMed: 38694373
DOI: 10.1097/MS9.0000000000001999 -
American Journal of Obstetrics &... Jun 2024Hepatic infarction is a rare complication of pregnancy most often associated with hemolysis, elevated liver enzymes, and low platelets syndrome. The objective of this... (Review)
Review
OBJECTIVE
Hepatic infarction is a rare complication of pregnancy most often associated with hemolysis, elevated liver enzymes, and low platelets syndrome. The objective of this review is to identify risk factors, present signs and symptoms, identify methods of diagnosis, and identify best management practices on the basis of published case reviews.
DATA SOURCES
PubMed and MEDLINE (Ovid) databases were searched for citations regarding hepatic infarction in pregnancy or the postpartum period from database inception until the study date of December 18, 2023. Key words included "liver infarction" or "hepatic infarction" and "pregnancy" or "obstetrics."
STUDY ELIGIBILITY CRITERIA
Case reviews or case series published in the English language were included. Our study was registered with the Prospective Register of Systematic Reviews (registration number CRD42023488176) and was conducted in accordance with the published Prospective Register of Systematic Reviews and Meta-analyses Of Observational Studies in Epidemiology guidelines.
METHODS
Included papers were evaluated for bias using a previously published tool.
RESULTS
A total of 38 citations documenting 50 pregnancies published between 1979 and 2023 were included. Of these, 34% had a history of hypertensive disease, 26% had antiphospholipid syndrome, and 22% had a history of thrombus. Of those without a preexisting diagnosis of antiphospholipid syndrome, 24% tested positive during hospitalization. Most patients presented with epigastric or right upper quadrant pain (78%), and 32% and 16% had severe blood pressure or mild blood pressure, respectively. Sixty-four percent of patients presented with transaminitis. Forty-six percent of patients delivered preterm, and 32% of pregnancies ended in intrauterine fetal demise, abortion, or early termination of pregnancy for maternal benefit. Computed tomography scans were used to confirm diagnosis of hepatic infarction in 58% of cases, magnetic resonance imaging in 14%, and ultrasound in 6%. In cases that described management, treatment was always multimodal, including antihypertensives (18%), therapeutic anticoagulation (45%), blood product transfusion (36%), plasma exchange or intravenous immunoglobulin (20%), and steroids (39%). Transfer to the intensive care unit was required in 20% of cases.
CONCLUSION
Hepatic infarction should be considered in all cases of hemolysis, elevated liver enzymes, and low platelets syndrome, but specifically in patients with a history of antiphospholipid syndrome who present with epigastric or right upper quadrant pain. The diagnosis can usually be confirmed with a computed tomography scan alone, and management should be prompt with supportive care, therapeutic anticoagulation, and steroids.
Topics: Humans; Pregnancy; Female; Infarction; Risk Factors; Antiphospholipid Syndrome; Pregnancy Complications; Liver; HELLP Syndrome
PubMed: 38621440
DOI: 10.1016/j.ajogmf.2024.101377 -
Antibodies (Basel, Switzerland) Mar 2024Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disorder, characterised by consistently high levels of antiphospholipid antibodies, thrombosis, and/or... (Review)
Review
Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disorder, characterised by consistently high levels of antiphospholipid antibodies, thrombosis, and/or pregnancy morbidity. Due to various suspected causes, deficient or insufficient levels of vitamin D in the serum have been reported in patients with PAPS; however, the reports have been sporadic and inconclusive. This systematic review and meta-analysis aimed to comprehensively evaluate the serum vitamin D levels in patients with PAPS compared to controls. A protocol was registered in PROSPERO (Registration No. CRD42019132128) and a systematic literature search was conducted through Google Scholar, PubMed, Web of Science, Scopus, and ScienceDirect databases without restricting language and year. Pooled prevalence, mean difference (MD), and odds ratio (OR) along with 95% confidence intervals (CI) were determined by using a random effects model. Study quality was assessed by the Joana Brigg's Institute (JBI) protocol and publication bias was evaluated by a trim and fill funnel plot, Begg's, and Egger's tests. The pooled prevalence of vitamin D deficiency and insufficiency was found to be 32.2% [95% CI: 16.3-48.2] and 61.5% [95% CI: 40.2-82.8], respectively. Serum levels of vitamin D were considerably lower in the PAPS patients compared to controls (MD: -5.75, 95% CI: -9.73 to -1.77; = 0.005). Multiple sensitivity analyses showed that the results remained statistically significant, demonstrating the robustness of this meta-analysis. No significant publication bias was detected in determining the MD of serum vitamin D levels in PAPS and controls. In conclusion, PAPS patients had greater rates of vitamin D deficiency or insufficiency, higher frequency of thrombosis, and lower serum vitamin D levels than healthy individuals.
PubMed: 38534213
DOI: 10.3390/antib13010022 -
Reumatologia Clinica Mar 2024This was a systematic review and meta-analysis of the prevalence of thromboembolic events in children and adolescents with antiphospholipid syndrome (APS). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIM
This was a systematic review and meta-analysis of the prevalence of thromboembolic events in children and adolescents with antiphospholipid syndrome (APS).
METHODS
We searched PubMed, EMBASE and Web of Science to select relevant articles published between 1 January 2000 and 27 February 2022. We used the random-effects meta-analysis to estimate pooled point prevalence rates of thromboembolic events in studies with a minimum sample size of 30.
RESULTS
We included five studies reporting data of 336 children and adolescents with primary APS and secondary APS (SAPS). Pooled point prevalence rates of initial general thrombosis, arterial thrombosis, venous thrombosis and stroke in individuals with seropositive APS were 98.2% (95% confidence interval [CI] 87.5-100), 27.6% (95% CI 21.4-34.2), 51.1% (95% CI 38.2-63.9) and 13.4% 95% CI (6.3-22.7), respectively. Pooled point prevalence rates of initial arterial and venous thromboses in children and adolescents with SAPS were 45.7% (95% CI 21.1-71.6) and 29.2% (95% CI 14.8-46), respectively.
CONCLUSION
Arterio-venous thromboembolism is highly frequent in children and adolescents with SAPS. More studies using thrombotic and non-thrombotic APS classification criteria are warranted to better assess the frequency and predictors of thromboembolism in age- and ancestry-diverse pediatric populations affected by different types of APS.
Topics: Child; Humans; Adolescent; Antiphospholipid Syndrome; Thrombosis; Venous Thrombosis; Venous Thromboembolism
PubMed: 38494306
DOI: 10.1016/j.reumae.2023.10.005 -
Clinical Immunology (Orlando, Fla.) Mar 2024Adrenal hemorrhage (AH) can occur in patients with antiphospholipid Syndrome (APS). We aimed to characterize the clinical manifestations, treatments, and outcomes of...
BACKGROUND
Adrenal hemorrhage (AH) can occur in patients with antiphospholipid Syndrome (APS). We aimed to characterize the clinical manifestations, treatments, and outcomes of patients presenting with APS-associated AH (APS-AH) through a retrospective cohort and a systematic literature review (SLR).
METHODS
We performed a mixed-source approach combining a multicenter cohort with an SLR of patients with incident APS-AH. We included patients from Mayo Clinic and published cases with persistent positivity for antiphospholipid antibodies and presenting with AH, demonstrated by imaging or biopsy. We extracted demographics, clinical characteristics, laboratory findings, treatment strategies, and outcomes (primary adrenal insufficiency and mortality). We used Kaplan-Meier and Cox models for survival analysis.
RESULTS
We included 256 patients in total, 61 (24%) from Mayo Clinic and 195 (76%) from the SLR. The mean age was 46.8 (SD 15.2) years, and 45% were female. 69% of patients had bilateral adrenal involvement and 64% presented adrenal insufficiency. The most common symptoms at presentation were abdominal pain in 79%, and nausea and vomiting 46%. Hyponatremia (77%) was the most common electrolyte abnormality. Factors associated with primary adrenal insufficiency were bilateral adrenal involvement at initial imaging (OR 3.73, CI; 95%, 1.47-9.46) and anticardiolipin IgG positivity (OR 3.80, CI; 95%, 1.30-11.09). The survival rate at five years was 82%. History of stroke was associated with 3.6-fold increase in mortality (HR 3.62, 95% CI; 1.33-9.85).
CONCLUSION
AH is a severe manifestation of APS with increased mortality. Most patients developed permanent primary adrenal insufficiency, particularly those positive for anticardiolipin IgG and bilateral adrenal involvement.
Topics: Female; Humans; Male; Middle Aged; Addison Disease; Antiphospholipid Syndrome; Hemorrhage; Immunoglobulin G; Multicenter Studies as Topic; Retrospective Studies; Adult
PubMed: 38244823
DOI: 10.1016/j.clim.2024.109906 -
Clinical Nutrition ESPEN Feb 2024Coenzyme Q10 (CoQ10) is a potent antioxidant and anti-inflammatory substance used to treat some rheumatic diseases. Our objective was to review the use of CoQ10 in... (Review)
Review
Coenzyme Q10 (CoQ10) is a potent antioxidant and anti-inflammatory substance used to treat some rheumatic diseases. Our objective was to review the use of CoQ10 in rheumatic diseases. PubMed/Medline, Embase, Scopus, and Web of Science databases were searched for articles on CoQ10 and rheumatic diseases between 1966 and April 2023. Twenty articles were found, including 483 patients. The investigated conditions were Fibromyalgia (FM) with 15 studies, Rheumatoid Arthritis (RA) with 3 studies, and Antiphospholipid Syndrome (APS) with 2 studies. After CoQ10 supplementation, RA patients observed improvements in disease activity index, inflammatory biomarkers (erythrocyte sedimentation rate), cytokine levels, and a decrease in malondialdehyde. In APS, CoQ10 improved endothelial function and decreased prothrombotic and proinflammatory mediators. Regarding FM, in most of the studies, the patients observed improvements in pain, fatigue, sleep, tender points count, mood disorders, and scores on the Fibromyalgia Impact Questionnaire (FIQ). The drug was well tolerated, with reports of minor side effects in two studies. CoQ10 supplementation seems to be efficacious as a complementary treatment for RA and FM. Upcoming studies with larger samples and including other rheumatic diseases are welcome.
Topics: Humans; Fibromyalgia; Ubiquinone; Antioxidants; Arthritis, Rheumatoid; Dietary Supplements
PubMed: 38220408
DOI: 10.1016/j.clnesp.2023.11.016 -
Lupus Jan 2024While the prevalence of antiphospholipid antibodies (aPL) in venous and arterial thrombotic events had already been estimated by previous studies, the prevalence of aPL...
BACKGROUND
While the prevalence of antiphospholipid antibodies (aPL) in venous and arterial thrombotic events had already been estimated by previous studies, the prevalence of aPL in subjects with Thrombotic Microangiopathy (TMA) is still not fully elucidated. Thus, we conducted a systematic review to estimate the frequency of aPL in subjects with biopsy-proven renal TMA.
METHODS
We conducted in the PubMed database a search for English-language studies investigating the presence of aPL in subjects with biopsy-proven renal TMA from January 1985 to December 2022. Keywords used in the search included: 'antiphospholipid syndrome', 'antiphospholipid antibodies' and 'thrombotic microangiopathy'. Cohorts of HUS patients were excluded due to the risk of over-estimating the prevalence of aPL in these populations. The median frequency for positive aPL including anticardiolipin antibodies (aCL), antibodies against β2-glycoprotein-I (anti-β2GPI) and lupus anticoagulant (LA) was then calculated.
RESULTS
522 articles were identified through the literature search. Six studies, assessing the prevalence of aPL in 211 subjects with renal TMA, were retrieved. The overall aPL prevalence was estimated as 24.4% (range 22-56). The estimated prevalence of aCL (IgG/IgM), anti-β2GPI, (IgG/IgM) and LA was 4.0% (range 3-27), 4.0% (range 3-16) and 18.9% (range 13-25), respectively. APS was diagnosed in 16.3% (range 11-29) of the patients. Of note, a high level of heterogeneity was observed when comparing the reported aPL profiles for each study.
CONCLUSIONS
This comprehensive systematic analysis of studies investigating the prevalence of aPL in renal TMA showed that, despite the high heterogeneity of the included studies, aPL are present in about one case out of four renal-TMA cases.
Topics: Humans; Antiphospholipid Syndrome; Antibodies, Antiphospholipid; Prevalence; Lupus Erythematosus, Systemic; Lupus Coagulation Inhibitor; Antibodies, Anticardiolipin; Thrombotic Microangiopathies; Immunoglobulin G; Immunoglobulin M
PubMed: 38116607
DOI: 10.1177/09612033231217351 -
Lupus Science & Medicine Oct 2023Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterised by venous thrombosis (VT) or arterial thrombosis (AT) and/or pregnancy morbidity and the... (Meta-Analysis)
Meta-Analysis
Therapy with direct oral anticoagulants for secondary prevention of thromboembolic events in the antiphospholipid syndrome: a systematic review and meta-analysis of randomised trials.
OBJECTIVE
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterised by venous thrombosis (VT) or arterial thrombosis (AT) and/or pregnancy morbidity and the presence of antiphospholipid antibodies. Direct oral anticoagulants (DOACs) hold several advantages to vitamin K antagonists (VKAs) for prevention of thrombosis and we wish to evaluate DOACs compared with VKAs in secondary prevention of thromboembolic events in patients with APS.
METHODS
We conducted searches of the published literature using relevant data sources (MEDLINE, Embase and Cochrane CENTRAL), and of trial registers for unpublished data and ongoing trials. We included randomised trials examining individuals >18 years with APS classified according to the criteria valid when the trial was carried out. Randomised controlled trials had to examine any DOAC agent compared with any comparable drug. We tabulated all occurrences of events from all eligible randomised trials. Due to few events, ORs and 95% CIs were calculated using the Peto method.
RESULTS
5 randomised trials comprising 624 patients met the predefined eligibility criteria. The primary outcome measure was new thrombotic events, a composite endpoint of any VT or AT, during the VKA-controlled phase of treatment. According to the I inconsistency index, there was evidence of statistical heterogeneity across the studies (I=60%). Across trials, 29 and 10 thrombotic events were observed in 305 and 319 patients with APS treated with DOAC and VKA, respectively, corresponding to a combined Peto OR of 3.01 (95% CI 1.56 to 5.78, p=0.001). There was a significantly increased risk of AT while treated with DOACs compared with VKA (OR 5.5 (2.5, 12.1) p<0.0001), but no difference in the risk of VT (p=0.87). We found no significant difference in risk of bleeding.
CONCLUSIONS
DOACs were associated with a significant increase in the risk of a new thrombotic event, especially AT, favouring standard prophylaxis with warfarin.
PROSPERO REGISTRATION NUMBER
CRD42019126720.
Topics: Humans; Antiphospholipid Syndrome; Secondary Prevention; Lupus Erythematosus, Systemic; Anticoagulants; Thrombosis; Randomized Controlled Trials as Topic
PubMed: 37899090
DOI: 10.1136/lupus-2023-001018 -
Clinical Immunology (Orlando, Fla.) Nov 2023Antiphospholipid syndrome (APS) is a systemic autoimmune disease clinically associated with thrombotic and obstetric events. Additional manifestations have been...
Clinical features, risk factors, and outcomes of diffuse alveolar hemorrhage in antiphospholipid syndrome: A mixed-method approach combining a multicenter cohort with a systematic literature review.
BACKGROUND
Antiphospholipid syndrome (APS) is a systemic autoimmune disease clinically associated with thrombotic and obstetric events. Additional manifestations have been associated with APS, like diffuse alveolar hemorrhage (DAH). We aimed to summarize all the evidence available to describe the presenting clinical features, their prognostic factors, and short- and long-term outcomes.
METHODS
We performed a mixed-method approach combining a multicenter cohort with a systematic literature review (SLR) of patients with incident APS-associated DAH. We described their clinical features, treatments, prognostic factors, and outcomes (relapse, mortality, and requirement of mechanical ventilation [MV]). Kaplan-Meier methods were used to estimate relapse and mortality rates, and Cox and logistic regression models were used to assess the factors associated as appropriate.
RESULTS
We included 219 patients with incident APS-associated DAH (61 from Mayo Clinic and 158 from SLR). The median age was 39.5 years, 51% were female, 29% had systemic lupus erythematosus, and 34% presented with catastrophic APS (CAPS). 74% of patients had a history of thrombotic events, and 26% of women had a history of pregnancy morbidity; half of the patients had a history of thrombocytopenia, and a third had valvulopathy. Before DAH, 55% of the patients were anticoagulated. At DAH onset, 65% of patients presented hemoptysis. The relapse rate was 47% at six months and 52% at one year. Triple positivity (HR 4.22, 95% CI 1.14-15.59) was associated with relapse at six months. The estimated mortality at one and five years was 30.3% and 45.8%. Factors associated with mortality were severe thrombocytopenia (< 50 K/μL) (HR 3.10, 95% CI 1.39-6.92), valve vegetations (HR 3.22, 95% CI 1.14-9.07), CAPS (HR 3.80, 95% CI 1.84-7.87), and requirement of MV (HR 2.22, 95% CI 1.03-4.80). Forty-two percent of patients required MV on the incident DAH episode. Patients presenting with severe thrombocytopenia (OR 6.42, 95% CI 1.77-23.30) or CAPS (OR 4.30, 95% CI 1.65-11.16) were more likely to require MV.
CONCLUSION
APS-associated DAH is associated with high morbidity and mortality, particularly when presenting with triple positivity, thrombocytopenia, valvular involvement, and CAPS.
Topics: Humans; Female; Adult; Male; Antiphospholipid Syndrome; Hemorrhage; Lung Diseases; Lupus Erythematosus, Systemic; Leukopenia; Risk Factors; Recurrence; Thrombocytopenia; Retrospective Studies; Multicenter Studies as Topic
PubMed: 37722463
DOI: 10.1016/j.clim.2023.109775