Factors associated with first thrombosis in patients presenting with obstetric antiphospholipid syndrome (APS) in the APS Alliance for Clinical Trials and International Networking Clinical Database and Repository: a retrospective study.

OBJECTIVE: To evaluate the subsequent rate of thrombosis among women with obstetric antiphospholipid syndrome (Ob-APS) in a multicentre database of antiphospholipid antibody (aPL)-positive patients, and the clinical utility of the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), a validated tool to assess the likelihood of developing new thrombosis, in this group of patients. DESIGN: Retrospective study. SETTING: The Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository. POPULATION: Women with Ob-APS. METHODS: Comparison of clinical and laboratory characteristics and measurement of aGAPSS in women with Ob-APS, with or without thrombosis, after initial pregnancy morbidity (PM). MAIN OUTCOME MEASURES: Risk factors for thrombosis and aGAPSS. RESULTS: Of 550 patients, 126 had Ob-APS; 74/126 (59%) presented with thrombosis, and 47 (63%) of these women developed thrombosis after initial PM, in a mean time of 7.6 ± 8.2 years (4.9/100 patient years). Younger age at diagnosis of Ob-APS, additional cardiovascular risk factors, superficial vein thrombosis, heart valve disease, and multiple aPL positivity increased the risk of first thrombosis after PM. Women with thrombosis after PM had a higher aGAPSS compared with women with Ob-APS alone [median 11.5 (4-16) versus 9 (4-13); P = 0.0089]. CONCLUSION: Based on a retrospective analysis of our multicentre aPL database, 63% of women with Ob-APS developed thrombosis after initial obstetric morbidity; additional thrombosis risk factors, selected clinical manifestations, and high-risk aPL profile increased the risk. Women with subsequent thrombosis after Ob-APS had a higher aGAPSS at entry to the registry. We believe that aGAPSS is a valid tool to improve risk stratification in aPL-positive women. TWEETABLE ABSTRACT: More than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity.

The anti-thrombotic effects of vitamin D and their possible relationship with antiphospholipid syndrome.

The importance of the immunomodulatory effects of vitamin D has recently been associated with autoimmune and chronic inflammatory diseases. Vitamin D deficiency has been linked to the development of autoimmune conditions. Antiphospholipid syndrome is an autoimmune disease characterized by thrombotic events and obstetric complications in patients with antiphospholipid antibodies. Current data show that patients with antiphospholipid syndrome have a high prevalence of vitamin D deficiency even without classic risk factors. Several studies have suggested vitamin D may have anti-thrombotic functions. In antiphospholipid syndrome, low vitamin D serum levels have been associated with thrombotic manifestations, suggesting a possible protective role of vitamin D in antiphospholipid syndrome. This literature review presents current evidence on the haemostatic functions of vitamin D and their possible relationship with the clinical manifestations of antiphospholipid syndrome.

Urinary neutrophil gelatinase-associated lipocalin and monocyte chemoattractant protein 1 as biomarkers for lupus nephritis in Colombian SLE patients.

Background Information regarding urinary biomarkers in Mestizo and Afro-Latin-American patients is very limited. We investigated whether levels of urinary neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemoattractant protein 1 (MCP-1) are good biomarkers to differentiate patients with lupus nephritis among Latin-American systemic lupus erythematosus (SLE) patients. Methods SLE patients meeting the revised American College of Rheumatology classification criteria for SLE were recruited. Urinary levels of NGAL and MCP-1 were measured using a commercial ELISA kit. Serum anti-C1q antibodies were measured by ELISA. SLE activity was measured with the systemic lupus erythematosus disease activity index (SLEDAI). Mann-Whitney tests were used to compare data and Spearman's rank correlations were used to examine associations between continuous variables. In addition, receiver operating characteristic curves were performed. Results One hundred and twenty SLE patients were recruited (87% women) with a median age of 32.8 ± 12.1 years and median disease duration of 7.3 ± 6.9 years. Afro-Latin-Americans had a significantly higher prevalence of lupus nephritis and higher SLEDAI scores than Mestizos. The three biomarkers were significantly higher in patients with lupus nephritis than in patients without lupus nephritis. In addition, urinary NGAL and MCP-1 were significantly higher in patients with active lupus nephritis than in inactive lupus nephritis. Urinary NGAL levels were significantly higher in Afro-Latin-American patients. A receiver operating characteristic curve for urinary biomarkers for lupus nephritis in all SLE patients showed a good level of sensitivity and specificity. Conclusion In our cohort of SLE patients, we found that urinary NGAL and MCP-1 in addition to anti-C1q antibodies were useful biomarkers for the identification of renal involvement and discrimination of active lupus nephritis among patients with renal disease.

The role of infectious diseases in the catastrophic antiphospholipid syndrome.

Catastrophic antiphospholipid syndrome (CAPS), also called "Asherson syndrome", is a variant of the antiphospholipid syndrome (APS) that occurs in less than 1% of APS cases. The etiology of CAPS is uncertain; however, several triggering factors have been recognized. The most common of these are infectious diseases, particularly those of the respiratory tract. CAPS pathogenesis is incompletely understood, but several theories have been proposed, such as the molecular mimicry theory, which describes the production of anti-ß2-glycoprotein I (GP1) antibody in response to infection. The process is complex and involves the activation of Toll-like receptor 4 (TLR-4), which triggers a cytokine storm, followed by endothelial alterations that induce a procoagulant state.

Carotid atherosclerosis is not associated with lower bone mineral density and vertebral fractures in patients with systemic lupus erythematosus.

BACKGROUND: Low bone mineral density (BMD) and vertebral fractures (VF) have been associated with atherosclerosis in the general population. We sought to investigate the relationship between BMD and VF and carotid atherosclerosis in women with systemic lupus erythematosus (SLE). METHODS: We studied 122 women with SLE. All patients had BMD, carotid intima-media thickness (IMT), and carotid artery atherosclerotic plaque assessment by ultrasound. RESULTS: Mean age at study entry was 44 years and mean disease duration was 11 years. Carotid plaque was found in 13 (11%) patients (9 postmenopausal and 4 premenopausal). Patients in the highest IMT quartile were more likely to be older (p = 0.001), have a higher body mass index (p = 0.008), and exhibit dyslipidemia at study entry (p = 0.041), compared with the lower three quartiles. BMD at the lumbar spine was lower in patients in the highest IMT quartile compared with the lower quartiles in the multivariate logistic analysis, however, there was no association between lumbar or total hip BMD and IMT (p = 0.91 and p = 0.6, respectively). IMT measurements did not differ according to the presence or absence of VF (0.08 ± 0.12 vs. 0.06 ± 0.03 mm, p = 0.11). A trend towards higher incidence of VF was found in patients with carotid plaque compared with those without (33% vs. 21%; p = 0.2). CONCLUSIONS: In patients with SLE, the presence of carotid atherosclerosis is not associated with low BMD or VF.

Lack of association between serum 25-hydroxyvitamin D levels and cervical human papillomavirus infection in systemic lupus erythematosus.

Our objective was to evaluate whether vitamin D deficiency is associated with cervical human papilloma virus (HPV) infection in women with SLE. This is a cross-sectional study of 67 women with SLE. A structured questionnaire was administered to ascertain the possible risk factors associated with cervical HPV infection. A gynaecological evaluation and cervical cytology screening were made. HPV detection and genotyping was made by PCR and linear array assay. Serum 25 hydroxyvitamin D levels were quantified by chemiluminescence immunoassay. Mean age and disease duration were 44.8 ± 10.6 and 42.5 ± 11.8 years, respectively. Demographic characteristics were similar in patients with and without deficiency (<20 ng/ml and ≥20 ng/ml). There were 28.4% of women with cervical HPV infection and 68.4% had high-risk HPV infections. Patients with 25 hydroxyvitamin D levels <20 ng/ml had a higher prevalence of cervical HPV infection than those with levels ≥20 ng/ml (30.7% vs. 25.8%; p = 0.72). We found no significant difference when high-risk HPV infection was evaluated (36.8% vs. 31.5%; p = 0.73). In conclusion, women with SLE have a high prevalence of vitamin D deficiency and cervical HPV infection. However, we found no association between vitamin D deficiency and cervical HPV.

Fracturas periprotésicas de cadera / Periprosthetic hip fractures

Durante la última década, las fracturas periprotésicas han aumentado su incidencia. La osteólisis, la edad y su función preoperatoria son factores que modifican la morbilidad. Las opciones de tratamiento incluyen tratamiento conservador y tratamiento quirúrgico. Objetivos: Presentar un estudio analizando los resultados funcionales del tratamiento quirúrgico de las fracturas periprotésicas de cadera en el Centro Médico ABC, tomando en cuenta variables preoperatorias y postoperatorias. Material y métodos: Estudio retrospectivo transversal de pacientes con diagnóstico de fracturas periprotésicas de cadera, entre Enero del 2000 y Diciembre del 2011, clasificadas con el sistema Vancouver. La escala de Oxford Hip Score se utilizó preoperatoriamente y postoperatoriamente como medida funcional. Las variables a evaluar son: edad, sexo, técnica quirúrgica empleada, tiempo de presentación entre la cirugía primaria y la fractura periprotésica. Resultados: Se analizaron 25 pacientes, la frecuencia fue de 3.3 casos por año. El 80% de las fracturas periprotésicas fueron postoperatorias, el 72% fueron artroplastías totales de cadera. El tiempo entre la cirugía primaria y el evento traumático fue de 2 a 4 años (68%), con promedio de 4.5 años en las hemiartroplastías y 3.9 años en las artroplastías totales. En la escala funcional (Oxford Hip Score) los calificados como buenos mantuvieron los mismos resultados; pacientes con calificación moderada se mantuvieron con 75% en la misma calificación. Los pacientes con calificación mala elevaron su funcionalidad. Conclusiones: En el Centro Médico ABC, el tratamiento de las fracturas periprotésicas de cadera mediante la valoración del Oxford Hip Score se considera con un desenlace bueno.

The incidence rate of periprosthetic fractures has increased in the past decade. Osteolysis, age and preoperative function are factors that influence morbidity. Treatment options include conservative and surgical treatment. Objectives: To conduct a study analyzing the functional results of the surgical treatment of periprosthetic hip fractures at the ABC Medical Center considering preoperative and postoperative variables. Material and methods: Cross-sectional retrospective study of patients with a diagnosis of periprosthetic hip fracture between January 2000 and December 2011, classified using the Vancouver system. The Oxford Hip Score was used pre- and postoperatively as a functional measure. The variables to evaluate included age, sex, surgical technique, and the time elapsed between primary surgery and the periprosthetic fracture. Results: Twenty-five patients were analyzed; frequency was 3.3 cases per year. 80% of periprosthetic fractures were postoperative; 72% were total hip arthroplasties. The time elapsed between primary surgery and the traumatic event was 2 to 4 years (68%), with a mean of 4.5 years for hemiarthroplasties and 3.9 years for total arthroplasties. Patients who according to the Oxford Hip Score had good function maintained their results; 75% of those with moderate function maintained their score. Patients with poor function improved. Conclusions: At the ABC Medical Center, the outcomes of the treatment of periprosthetic hip fractures are considered as good according to the Oxford Hip Score.

[Periprosthetic hip fractures]. / Fracturas periprotésicas de cadera.

UNLABELLED: The incidence rate of periprosthetic fractures has increased in the past decade. Osteolysis, age and preoperative function are factors that influence morbidity. Treatment options include conservative and surgical treatment. OBJECTIVES: To conduct a study analyzing the functional results of the surgical treatment of periprosthetic hip fractures at the ABC Medical Center considering preoperative and postoperative variables. MATERIAL AND METHODS: Cross-sectional retrospective study of patients with a diagnosis of periprosthetic hip fracture between January 2000 and December 2011, classified using the Vancouver system. The Oxford Hip Score was used pre- and postoperatively as a functional measure. The variables to evaluate included age, sex, surgical technique, and the time elapsed between primary surgery and the periprosthetic fracture. RESULTS: Twenty-five patients were analyzed; frequency was 3.3 cases per year. 80% of periprosthetic fractures were postoperative; 72% were total hip arthroplasties. The time elapsed between primary surgery and the traumatic event was 2 to 4 years (68%), with a mean of 4.5 years for hemiarthroplasties and 3.9 years for total arthroplasties. Patients who according to the Oxford Hip Score had good function maintained their results; 75% of those with moderate function maintained their score. Patients with poor function improved. CONCLUSIONS: At the ABC Medical Center, the outcomes of the treatment of periprosthetic hip fractures are considered as good according to the Oxford Hip Score.

Delayed lupus nephritis.

OBJECTIVE: To describe and analyse the clinical and immunological characteristics of a large series of patients with delayed lupus nephritis (LN). METHODS: A cross-sectional study was carried out. Patients with systemic lupus erythematosus (SLE) who developed renal involvement >or=5 years after the first manifestation(s) of the disease (delayed LN, n = 48) were compared with patients with SLE in whom LN developed within 5 years or less after SLE appeared (early-onset LN, n = 187). A control group, the no LN (NLN) group, comprised patients with longstanding SLE (duration of disease >10 years) who had never shown signs of renal involvement (n = 164). RESULTS: The group with delayed LN was positively associated with Sjögren's syndrome, lung involvement and antiphospholipid syndrome as compared with early LN. However, its renal clinical expression and histopathological patterns were similar to those of early-onset LN. The frequency of anti-dsDNA, anti-Sm and anti-RNP antibodies was higher in patients with LN than in the NLN group, as was the frequency of low complement levels. Jaccoud's arthropathy was a protective factor for nephritis. CONCLUSIONS: Delayed LN is not uncommon in patients with SLE. The identified risk factors might aid in its diagnosis and enhance the ability to identify patients at risk for this complication of SLE.

Antiphospholipid syndrome in Latin American patients: clinical and immunologic characteristics and comparison with European patients.

The objective of this study was to analyse the prevalence and characteristics of the main clinical and immunological manifestations at the onset and during the evolution of the disease in a cohort of patients from Latin America (mainly of mestizo origin) and to compare the Latin American with the European patients. Clinical and serological characteristics of 100 APS patients from Mexico and Ecuador were collected in a protocol form that was identical to that used to study the ;Euro-Phospholipid' cohort. The cohort consisted of 93 female patients (93.0%) and seven (7.0%) male patients. There were 91 mestizos (91.0%), seven whites (7.0%) and two Amerindians (2.0%). The most common manifestations were livedo reticularis (40.0%), migraine (35.0%), inferior extremity deep vein thrombosis (32.0%), thrombocytopenia (28.0%) and hemolytic anemia (20.0%). Several clinical manifestations were more prevalent in Latin American than in European patients and they included mainly neurological (migraine, transient global amnesia, acute ischemic encephalopathy, amaurosis fugax) and cutaneous (livedo reticularis, skin ulcerations, superficial cutaneous necrosis, multiple subungual splinter hemorrhages) manifestations as well as hemolytic anemia. The APS has a wide variety of clinical and immunological manifestations at the onset and during the evolution of the disease and the ethnic origin in addition to environmental and socioeconomic factors can modify the disease expression.

Lack of subclinical myocardial ischaemia in Mexican patients with systemic lupus erythematosus without traditional risk factors for coronary artery disease.

The objective of this study was to analyse whether patients with systemic lupus erythematosus (SLE) without traditional risk factors for coronary artery disease (CAD) develop subclinical myocardial ischaemia in the first years after diagnosis. A cross-sectional analysis of a cohort of 200 female SLE patients was conducted. We selected those patients who fulfilled the American College of Rheumatology (ACR) SLE criteria and had no traditional risk factors for CAD, including diabetes mellitus, hypertension, obesity, hyperlipidemia, and smoking. After an initial clinical and laboratory examination, patients were evaluated using a baseline echocardiogram and a dobutamine and atropine stress echocardiogram to search for subclinical myocardial ischaemia. Forty-one patients were included in the study. The mean age at the time of the study was 34.5 +/- 9.56 years (mean +/- SD). The mean age at diagnosis was 30.3 +/- 9.39 years. The mean time from diagnosis was 3.9 +/- 3.3 years. Baseline disease activity index (MEX-SLEDAI score) showed that 92.6% of patients had disease activity, although most patients had mild activity. A dobutamine and atropine stress echocardiogram was performed in 40 patients. All 40 patients had negative tests for subclinical myocardial ischaemia. Patients without traditional risk factors for CAD do not have an increased risk for subclinical myocardial ischaemia in the first years after diagnosis. A longitudinal follow-up study of these patients is needed to confirm our findings and assess if additional non-traditional risk factors for CAD increase the risk for myocardial ischaemia.

[Intolerance to hydroxychloroquine marketed in Spain (Dolquine) in patients with autoimmune conditions]. / Intolerancia a la hidroxicloroquina comercializada en España (Dolquine) en pacientes con patología autoinmune.

BASIS: A significant proportion of our patients has described to have problems from tolerance to Dolquine, a new presentation of hydroxychloroquine recently marketed in Spain, compared to Plaquenil. The objective was to know the tolerability and the adverse effects of this new presentation. PATIENTS AND METHOD: A cross-sectional multicenter study on 133 patients treated with Dolquine was conducted. RESULTS: Of the 133 patients (87% women; average age [AA]: 32.9 [15.4] years) who received Dolquine during an average period of 6.7 (1.4) months, 32 patients (24%) described to have more problems with this drug in comparison with other antimalarial. The adverse effects experienced were: bitter taste (62.4%), difficulty in swallowing the tablet (13.5%), dyspepsia (9.8%), nausea (7.5%), vomiting (1.5%), pruritus (1.5%), diarrhea (0.7%), and instability feeling (0.7%). The presence of gastrointestinal adverse effects was not related to the consumption of gastroerosive drugs, gastric protectors, or a high number of drugs. The attrition rate was 9.8%. Conclusions. Dolquine induces lower tolerance and more gastrointestinal adverse effects than Plaquenil, pointing out its bitter taste and the difficulty in swallowing it. Despite this higher intolerance there was not an increase in the attition rate from the antimalarial treatment in comparison to other series.

Prophylaxis of the antiphospholipid syndrome: a consensus report.

Hypothetical circumstances that may require prophylaxis for a potential antiphospholipid syndrome (primary prophylaxis), or in some instances when there already had been some manifestations ofthe syndrome (secondary prophylaxis), were presented to a panel of experts for their consideration on potential prophylactic intervention. These were subsequently presented to the participants in the First International Consensus on Treatment of the Antiphospholipid Syndrome. In most instances there was consensus in adding low dose aspirin, an exception being aspirin allergy when other antiaggregants could be used in nonpregnant subjects. General measures to prevent thrombosis and other vasoprotective actions should also be provided. Higher risk of fetal loss or thrombosis called for anticoagulation with coumadin in nonpregnant subjects or subcutaneous low molecular weight heparin in pregnant ones. When indicated, prophylaxis of the antiphospholipid syndrome should be provided in systemic lupus erythematosus patients who are being treated for their disease. In no instance should corticosteroids or immunosuppresants be given as prophylactic of an antiphospholipid syndrome.

Catastrophic antiphospholipid syndrome: clinical description and triggering factors in 8 patients.

In 1992, an attempt to single out a different and important group of patients was adopted by introducing the term "catastrophic" antiphospholipid syndrome (APS) to describe their potentially life threatening clinical course, characterized by acute multiorgan failure (3 or more organ systems damaged). Patients previously described in the literature showed certain differences that appear to distinguish this minority group of patients with catastrophic APS from the majority of APS patients. We describe 8 patients with catastrophic APS, focusing especially on the possible extrinsic factors (mainly infections) that might trigger this "catastrophic" situation.