RESUMO
OBJECTIVES: We aimed to evaluate the prevalence of non-criteria clinical features in patients with primary antiphospholipid syndrome (APS), and to assess their relationship to thrombosis and damage. METHODS: We retrospectively included 177 primary APS patients, and/or patients who only achieved the serological Sydney criteria but had thrombocytopenia and/or haemolytic anaemia. We registered demographics, serology, treatment, thrombotic/obstetric manifestations and non-criteria clinical manifestations (cutaneous, haematologic, renal, heart valve disease, and neurological). We scored the DIAPS and a modified SLICC index. We used logistic regression and reported OR with 95% CI. RESULTS: 78% were women with a median follow-up of 6.7 years. Thrombosis was found in 74% of patients, 29.3% had obstetric features, and 64% had non-criteria clinical manifestations. The frequency of the non-criteria clinical manifestation was: haematologic 40.1%, cutaneous 20.9%, neurologic 18%, cardiac 5% and renal 4.5%. Non-criteria features were associated with LA (OR 2.3, 95% 1.03-5.1) and prednisone use (OR 8.2, 95% CI 1.7-39.3). A DIAPS score ≥1 was associated with thrombosis (OR 53.1, 95% CI 17.8-15.2), prednisone use (OR 0.27, CI 95% 0.09-0.83) and neurological involvement (OR 6.4, 95% CI 1.05-39.8); whereas a modified SLICC ≥ 1 with thrombosis (OR 10.2; IC 95% 4.43-26.1), neurological involvement (OR 6.4, 95%CI 1.05-39.8), obstetric features (OR 0.32 CI 95% 0.12-0,81) and cutaneous features (OR 5.3, CI 95% 1.4-19), especially livedo reticularis (OR 5.45; IC 95% 1.49-19.8). CONCLUSIONS: Non-criteria clinical manifestations are common and associated with LA. Among them, neurologic involvement and the presence of livedo were associated with damage accrual.
Assuntos
Síndrome Antifosfolipídica , Trombose , Humanos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Feminino , Estudos Retrospectivos , Adulto , Masculino , Pessoa de Meia-Idade , Trombose/etiologia , Trombose/epidemiologia , Fatores de Risco , Prevalência , Razão de Chances , Modelos Logísticos , Anemia Hemolítica/etiologia , Anemia Hemolítica/epidemiologia , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Nefropatias/epidemiologia , Nefropatias/etiologia , Nefropatias/diagnóstico , Prednisona/uso terapêutico , Prognóstico , Fatores de Tempo , Anticorpos Antifosfolipídeos/sangueRESUMO
OBJECTIVE: We aimed to evaluate the frequency of obstructive sleep apnea (OSA) in patients with thrombotic primary antiphospholipid syndrome (tPAPS), to investigate the performance of screening tools for OSA in this scenario and to compare clinical/laboratorial differences in tPAPS patients with and without OSA. METHODS: We consecutively enrolled patients with tPAPS to undergo sleep studies using a portable monitor. OSA was defined as apnea-hypopnea index ≥15 events/h. Frequency of OSA in tPAPS was evaluated and compared with age-, gender-, and BMI-matched controls (1:3 ratio) from the Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Next, we tested the performance of three different screening tools for assessing OSA in patients with tPAPS. Finally, patients with tPAPS were stratified according to OSA status comparing their clinical and laboratory characteristics (including damage burden measured by Damage Index for Antiphospholipid Syndrome [DIAPS] and biomarkers associated with thrombosis) using standard statistical procedures. RESULTS: Fifty-two patients were included for analysis (females: 82.7%; mean age: 48 ± 14 years; body-mass index: 31.1 ± 6.5 Kg/m2; 25% with moderate-severe OSA). When compared to matched controls from ELSA-Brasil (n = 115), there was no significant differences in the frequencies of OSA (tPAPS: 12/42 [28.6%] vs. controls: 35/115 [30.4%], p = 0.821). Among screening tools, NoSAS had the highest area under ROC curve (AUC 0.806, CI 95% 0.672-0.939, p = 0.001), followed by STOP-Bang (AUC 0.772, CI 95% 0.607-0.938, p = 0.004). Patients with comorbid tPAPS and OSA presented higher levels of von Willebrand factor (vWF) (median 38.9 vs. 32.6, p = 0.038) and DIAPS (median 5 vs. 2, p = 0.020), when compared to those without OSA. OSA remained statistically associated with higher DIAPS, even after controlling for age, disease duration and BMI. CONCLUSION: OSA is common in patients with tPAPS, with rates comparable to a non-referred population. Both NoSAS and STOP-Bang scores seems to be useful for screening OSA in these patients. Patients with tPAPS+OSA had higher damage burden and higher levels of vWF, which might suggest a more severe phenotype of tPAPS in this scenario.
Assuntos
Síndrome Antifosfolipídica , Apneia Obstrutiva do Sono , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Síndrome Antifosfolipídica/epidemiologia , Síndrome Antifosfolipídica/complicações , Fator de von Willebrand , Apneia Obstrutiva do Sono/epidemiologia , Comorbidade , Inquéritos e Questionários , FenótipoRESUMO
OBJECTIVES: The antiphospholipid syndrome (APS) is an autoimmune disease associated with thrombotic and non-thrombotic neurologic manifestations. APS is classified as primary (PAPS) or secondary (SAPS) when it co-exists with another autoimmune disease. We aim to describe the spectrum of acute cerebrovascular disease among patients with APS, their differences between stroke subtypes, and long-term functional outcomes. METHODS: Retrospective cohort study including adult (≥18 years) patients with APS followed in the stroke clinic of a tertiary-care reference center for autoimmune diseases in Mexico from 2009 to 2019. RESULTS: We studied 120 cases; 99 (82.5%) women; median age 43 years (interquartile range 35-52); 63.3% with SAPS. Demographics, comorbidities, and antiphospholipid antibodies (aPL) positivity were similar between APS type and stroke subtypes. Amongst index events, we observed 84 (70%) acute ischemic strokes (AIS), 19 (15.8%) cerebral venous thromboses (CVT), 11 (9.2%) intracerebral hemorrhages (ICH), and six (5%) subarachnoid hemorrhages (SAH). Sixty-seven (55.8%) were known patients with APS; the median time from APS diagnosis to index stroke was 46 months (interquartile range 12-96); 64.7% of intracranial hemorrhages (ICH or SAH) occurred ≥4 years after APS was diagnosed (23.5% anticoagulation-related); 63.2% of CVT cases developed before APS was diagnosed or simultaneously. Recurrences occurred in 26 (22.8%) patients, AIS, in 18 (69.2%); intracranial hemorrhage, in eight (30.8%). Long-term functional outcomes were good (modified Rankin Scale ≤2) in 63.2% of cases, during follow-up, the all-cause mortality rate was 19.2%. CONCLUSION: We found no differences between stroke subtypes and APS types. aPL profiles were not associated with any of the acute cerebrovascular diseases described in this cohort. CVT may be an initial thrombotic manifestation of APS with low mortality and good long-term functional outcome.
Assuntos
Síndrome Antifosfolipídica , Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Trombose , Adulto , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Hemorragia Cerebral/patologia , Feminino , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Trombose/epidemiologia , Trombose/etiologiaRESUMO
BACKGROUND: Characteristics of primary APS (PAPS) in the youth population have never been studied. In contrast with children, pregnancy is genuinely relevant in the youth age, and understanding clinical characteristics of PAPS patients within this specific age stratum may also provide insights regarding the well-known risk of poor obstetric outcomes during the adolescence. OBJECTIVE: To evaluate clinical and laboratory characteristics of patients with youth-onset PAPS (15-24 years) and compare them with adult-onset PAPS (over 24 years old). METHODS: This was a cross-sectional study derived from two rheumatology outpatient clinics. Patients who fulfilled Sidney criteria and who were 15 years of age or older at disease onset were included. Secondary APS patients were excluded. We subdivided patients into two groups: youth- (15-24 years) and adult-onset (over 24 years) and compared them regarding demographic characteristics, criteria and non-criteria manifestations, cardiovascular risk factors, and aPL status. For the pregnancy outcomes analysis, ever-pregnant patients were divided in three groups: youth-onset, early adult-onset (25-34 years), and late adult-onset (35-49 years). RESULTS: A total of 250 consecutive PAPS patients were included. Groups had a comparable female and Caucasian distribution. We found a similar disease duration (14.0±7.9 vs 17.0±10.1 years, p = 0.079) and similar rates of thrombotic arterial (34.2% vs. 42.0%, p = 0.250) and venous events (69.7% vs. 69.5%, p = 0.975) between them. Skin ulcers were more frequent in the youth-onset group (17.1% vs. 4.0%, p = 0.001), whereas nephropathy was less common (1.3% vs. 8.0%, p = 0.039). No differences were observed for the other criteria and non-criteria manifestations. The adult-onset group presented more frequently with hypertension (p = 0.002), hyperlipidemia (p = 0.008), and smoking (p = 0.003). The youth-onset group presented a higher frequency of obstetric events as the first manifestation of PAPS (30.3% vs. 21.7%, p = 0.005), with worse pregnancy outcomes, namely, fetal death (58.5% vs. 46.4% vs. 24.1%, p = 0.012) and premature delivery (35.8% vs. 19.0% vs. 10.3%, p = 0.016). Of note, all groups had a comparable number of pregnancies (2.81±2.52 vs 2.74±2.07, p = 0.899). CONCLUSION: This study provides novel evidence that youth-onset PAPS presents a higher frequency of obstetric complications as its first manifestation, with an increased risk of fetal death and preterm delivery. Early recognition of this condition by obstetricians is essential to improve prognosis.
Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Aborto Espontâneo/epidemiologia , Adolescente , Adulto , Idade de Início , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Estudos Transversais , Feminino , Morte Fetal , Humanos , Recém-Nascido , Lúpus Eritematoso Sistêmico/epidemiologia , Pessoa de Meia-Idade , Gravidez , Úlcera Cutânea/epidemiologia , Adulto JovemAssuntos
Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/diagnóstico , Ácido Úrico/sangue , Adulto , Fatores Etários , Anticorpos Anticardiolipina/sangue , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/epidemiologia , Dislipidemias/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Inibidor de Coagulação do Lúpus/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores SexuaisAssuntos
Síndrome Antifosfolipídica/epidemiologia , Trombofilia/epidemiologia , Adulto , Feminino , Humanos , Masculino , PrevalênciaRESUMO
OBJECTIVE: The objective of this study was to identify clinical and laboratory risk factors for ischemic stroke (IS) in primary antiphospholipid syndrome (APS) patients. MATERIALS AND METHODS: We performed a case-control study with consecutive primary APS patients divided into two groups, those who presented with IS, vs. those with no history of stroke. Demographics, vascular risk factors, therapeutic approaches, laboratory, imaging and functional outcomes were recorded. RESULTS: Fifty-three confirmed primary APS patients with IS and sixty-six non-stroke primary APS controls were recruited. Most patients were female (65.5 %), with a median age of 33 years. The main vascular risk factors for primary APS-associated stroke were hypertension (11.3 %), diabetes (11.3 %) and hypercholesterolemia (9.4 %). Among patients with stroke, median NIHSS score was 6; 15.1 % of these patients presented a recurrent stroke, and 88.8 % had a good functional outcome at the final follow-up. Positive lupus anticoagulant (OR = 6.1, 95 %CI 2.7-13.5), anti-ß2 glycoprotein IgG (OR = 3.6, 95 %CI 1.7-7.9), and anticardiolipin IgG (OR = 2.8, 95 %CI 1.3-5.9) were more prevalent in non-stroke primary APS, with a triple-positive antibody presence in 46.4 % of controls vs. 22.2 % of patients with stroke (OR = 3.0, 95 %CI 1.3-6.7). At the time of the index event (arterial or venous), 14 known primary APS patients were using vitamin K antagonists, but only 35.7 % of them had achieved therapeutic INR. CONCLUSION: Patients with primary APS and IS have similar vascular risk factors and lower antibody positivity than those with extracranial thrombosis.
Assuntos
Síndrome Antifosfolipídica/epidemiologia , AVC Isquêmico/epidemiologia , Adulto , Anticorpos Anticardiolipina/imunologia , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/imunologia , Estudos de Casos e Controles , Diabetes Mellitus/epidemiologia , Feminino , Estado Funcional , Humanos , Hipercolesterolemia/epidemiologia , Hipertensão/epidemiologia , Coeficiente Internacional Normatizado , AVC Isquêmico/etiologia , AVC Isquêmico/imunologia , AVC Isquêmico/fisiopatologia , Inibidor de Coagulação do Lúpus/imunologia , Masculino , Isquemia Mesentérica/epidemiologia , Isquemia Mesentérica/etiologia , Oclusão Vascular Mesentérica/epidemiologia , Oclusão Vascular Mesentérica/etiologia , Pessoa de Meia-Idade , Veia Porta , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , Fatores de Risco , Trombose Venosa/epidemiologia , Trombose Venosa/etiologiaRESUMO
OBJECTIVE: To assess childhood-onset systemic lupus erythematosus-related antiphospholipid syndrome(cSLE-APS) in a large Brazilian population. METHODS: A retrospective observational cohort study was carried-out in 27 Pediatric Rheumatology university centers, including 1519 cSLE patients. RESULTS: cSLE-APS was observed in 67/1519 (4%) and was diagnosed at disease onset in 39/67 (58%). The median disease duration was 4.9 (0-17) years. Thrombosis recurrences were evidenced in 18/67 (27%) cSLE-APS patients. The most frequent thrombosis sites in cSLE-APS patients were: venous thrombosis in 40/67 (60%), especially deep vein thrombosis in 29/40 (72%); arterial thrombosis in 35/67 (52%), particularly stroke; small vessels thrombosis in 9/67 (13%) and mixed thrombosis in 3/67 (4%). Pregnancy morbidity was observed in 1/67 (1%). Non-thrombotic manifestation associated to cSLE-APS occurred in 21/67 (31%), mainly livedo reticularis in 14/67 (21%), valvar thickening in 4/67 (6%) and valvar vegetations not related to infections in 2/67 (3%). None of them had catastrophic APS. Further analysis demonstrated that the median of SLICC/ACR-DI [1(0-5) vs. 0(0-7),pâ¯<â¯0.0001] was significantly higher in cSLE-APS patients compared to cSLE without APS. The frequencies of cerebrovascular disease (40% vs. 1%,pâ¯<â¯0.0001), polyneuropathy (9% vs. 1%,pâ¯<â¯0.0001), SLICC/ACR-DI ≥1 (57% vs. 27%, pâ¯<â¯0.0001) and intravenous cyclophosphamide use (59% vs. 37%, pâ¯<â¯0.0001) were significantly higher in the former group. CONCLUSIONS: Our large multicenter study demonstrated that cSLE-APS was a rare condition, occurring during disease course with a high accrual damage. Central and peripheral neuropsychiatric involvements were distinctive features of this autoimmune thrombosis.
Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Complicações na Gravidez , Adulto , Idade de Início , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Brasil/epidemiologia , Criança , Estudos de Coortes , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Morbidade , Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVE: Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease, and in some conditions, admission to the intensive care unit (ICUs) is required. This study describes the clinical and prognostic factors in SLE patients admitted to the ICU. METHODS: We conducted a retrospective study that reviewed all clinical records of patients with SLE admitted to the ICU between 2011 and 2018. RESULTS: We evaluated 188 patients, with 279 ICU admissions. Most patients were female (n = 159; 84.57%) with a median age of 35 years (interquartile range (IQR) = 25-48 years). Infection was the leading cause of admission in 77 (27.60%) cases, followed by lupus flare. The average length of hospitalization was 5 days (IQR 3-11 days), and the SLE Disease Activity Index 2000, Acute Physiology, Age and Chronic Health Evaluation (APACHE II), and Sequential Organ Failure Assessment (SOFA) scores were 9 (IQR 2-17), 14 (IQR 10-17), and 3 (IQR 2-5), respectively. Non-survivors presented with higher APACHE II and SOFA scores. Infection was the leading cause of mortality (n = 38; 20.21%), and predictors of mortality included invasive mechanical ventilation, vasoactive medication requirement, higher SOFA scores, and antiphospholipid syndrome comorbidity. CONCLUSIONS: We found that infection was the leading cause of ICU admissions and mortality in patients with SLE. Factors identified here as predictors of mortality should be accurately identified at admission for the prompt treatment of SLE patients.
Assuntos
Unidades de Terapia Intensiva/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/epidemiologia , APACHE , Adulto , Síndrome Antifosfolipídica/epidemiologia , Colômbia/epidemiologia , Comorbidade , Cuidados Críticos , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Escores de Disfunção Orgânica , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Exacerbação dos SintomasRESUMO
This is a review of scientific publications on renal involvement in antiphospholipid syndrome (APS), with focus on clinical and histopathological findings and treatment. A search for English-language articles on renal involvement in APS covering the period 1980-2017 was conducted in Medline/PubMed and Scopus databases using the MeSH terms "antiphospholipid syndrome", "antiphospholipid antibodies", "glomerulonephritis" and "thrombotic microangiopathy" (TMA). APS nephropathy is primarily the result of thromboses in renal arteries or veins, intraparenchymatous arteries and glomerular capillaries. On histology, APS nephropathy is characterized by TMA, but chronic vaso-occlusive lesions are also commonly observed (fibrous intimal hyperplasia, focal cortical atrophy, fibrous occlusions of arteries). Anticardiolipin and lupus anticoagulant are the most prevalent antibodies in patients with APS nephropathy. The spectrum of renal manifestations includes renal vein thrombosis, renal artery thrombosis/stenosis, TMA, increased allograft vascular thrombosis and malignant hypertension. Anticoagulation is the standard treatment of thrombotic events. In systemic lupus erythematosus (SLE) patients with antiphospholipid antibodies (aPL), kidney failure due to SLE nephritis (immune-complex disease) should be clearly distinguished from kidney failure due to APS-related TMA. In such cases, renal biopsy is mandatory. SLE nephritis requires immunosuppressive therapy, whereas APS nephropathy is usually treated with anticoagulants. Recently, eculizumab and sirolimus have been proposed as a rescue therapy. Based on our review, APS nephropathy appears to be a distinct clinical condition. TMA is a characteristic histopathological finding in APS and is strongly associated with the presence of aPL. This has important therapeutic implications and allows distinguishing APS nephropathy from lupus nephritis.