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OBJECTIVE: To assess organ damage, with emphasis on the cardiovascular system, over the different stages of the disease in a large SLE cohort. METHODS: Multicentre, longitudinal study of a cohort of 4219 patients with SLE enrolled in the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We longitudinally analysed SDI (globally and for each domain) over time only in the 1274 patients whose dates of damage events had been recorded. RESULTS: During the first year after diagnosis of SLE, 20% of the 1274 patients presented with new damage manifestations. At years 2 and 3, new damage was recorded in 11% and 9% of patients. The annual percentage of patients with new damage after year 5 decreased to 5%. In the first year with the disease, most damage was accumulated in the musculoskeletal, neuropsychiatric and renal systems; in later stages, most damage was in the musculoskeletal, ocular and cardiovascular systems. Considering 'cerebrovascular accident' and 'claudication for 6 months' as cardiovascular items, the cardiovascular system was the second most affected system during the early stages of SLE, with 19% of the patients who presented with damage affected at first year after diagnosis. During the late stages, 20-25% of the patients presenting with new damage did so in this modified cardiovascular domain of the SDI. CONCLUSIONS: New damage occurs mainly during the first year following diagnosis of SLE. Cardiovascular damage is relevant in both the early and the late stages of the disease. Strategies to prevent cardiovascular damage should be implemented early after diagnosis of SLE.
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Sistema Cardiovascular , Lúpus Eritematoso Sistêmico , Sistema de Registros , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Estudos Longitudinais , Masculino , Feminino , Adulto , Espanha/epidemiologia , Pessoa de Meia-Idade , Sistema Cardiovascular/fisiopatologia , Doenças Cardiovasculares/epidemiologia , Índice de Gravidade de Doença , Progressão da Doença , ReumatologiaRESUMO
Inherited thrombophilia (IT) has been implicated as a potential causal factor of adverse pregnancy outcomes (APOs), including recurrent miscarriage with and without the presence of antiphospholipid syndrome (APS). The aim of this study was to assess the prevalence and impact of IT on fetal-maternal outcomes and thrombotic risk in women within the spectrum of obstetric APS. Three hundred and twenty-eight women with APS-related obstetric morbidity ever pregnant were included. Of these, 74 met the APS classification criteria, 169 were non-criteria (NC)-APS, and 85 were seronegative (SN)-APS. Patients with other autoimmune diseases were excluded. APOs included early pregnancy loss, fetal death, preeclampsia, abruptio placentae, and preterm birth. Successful pregnancy was defined as the achievement of a live newborn. A literature search was also performed. The mean age of the overall group was 33.9 ± 5.3 years, and the patients were followed up for 35 (11-79) months. During the study period, there were 1332 pregnancies. Nearly 14% of the patients had an associated IT. IT patients more frequently received the standard-of-care (SoC) therapy. The presence of IT was not associated with worse maternal-fetal outcomes in patients treated with SoC treatment. Overall, IT patients had a lower frequency of newborns without treatment, especially those without definite APS. In addition, IT did not increase the risk of thrombosis during pregnancy or the postpartum period. A detailed analysis of the literature review identified only four publications related to our study and did not show conclusive evidence of the impact of IT on patients with obstetric APS. The group of women with APS-related obstetric morbidity and IT who did not receive treatment, especially those without definite APS, had a worse prognosis in terms of a live birth. However, with SoC therapy, the prognosis is similar in those patients without IT. The association of IT with APS does not seem to predispose to the development of thrombosis during pregnancy and/or the postpartum period.
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Autoantibodies are the hallmark of autoimmunity, and specifically, antinuclear antibodies (ANA) are one of the most relevant antibodies present in systemic autoimmune diseases (AID). In the present study, we evaluate the relationship between ANA and sociodemographic and biobehavioral factors in a population with a low pre-test probability for systemic AID. ANA were determined in serum samples at baseline visit from 2997 participants from the Camargo Cohort using indirect immunofluorescence assay, and two solid phase assays (SPA), addressable laser bead immunoassay, and fluorescence enzyme immunoassay. Sociodemographic and biobehavioral features of the subjects were obtained at baseline visit using a structured questionnaire. The prevalence of ANA positive results was significantly higher when indirect immunofluorescence assay was used as screening method in comparison with SPAs, being higher in females, older subjects, and those with higher C-reactive protein levels. Considering biobehavioral features, the prevalence was higher in those individuals with a sedentary lifestyle, and in ex- and non-alcohol users. Moreover, considering the relevance of the antibody load using ANA Screen, the prevalence of the antibody load also increased with age, especially in females. In conclusion, the prevalence of ANA varies depending on sociodemographic and biobehavioral features of the subjects, which could be relevant specifically in a population with a low pre-test probability for systemic AIDs.
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INTRODUCTION: Obstetric complications are more common in women with systemic lupus erythematosus (SLE) than in the general population. OBJECTIVE: To assess pregnancy outcomes in women with SLE from the RELESSER cohort after 12 years of follow-up. METHODS: A multicentre retrospective observational study was conducted. In addition to data from the RELESSER register, data were collected on obstetric/gynaecological variables and treatments received. The number of term pregnancies was compared between women with pregnancies before and after the diagnosis of SLE. Further, clinical and laboratory characteristics were compared between women with pregnancies before and after the diagnosis, on the one hand, and with and without complications during pregnancy, on the other. Bivariate and multivariate analyses were carried out to identify factors potentially associated with complications during pregnancy. RESULTS: A total of 809 women were included, with 1869 pregnancies, of which 1395 reached term. Women with pregnancies before the diagnosis of SLE had more pregnancies (2.37 vs 1.87) and a higher rate of term pregnancies (76.8% vs 69.8%, p < 0.001) compared to those with pregnancies after the diagnosis. Women with pregnancies before the diagnosis were diagnosed at an older age (43.4 vs 34.1 years) and had more comorbidities. No differences were observed between the groups with pregnancies before and after diagnosis in antibody profile, including anti-dsDNA, anti-Sm, anti-Ro, anti-La, lupus anticoagulant, anticardiolipin or anti-beta-2-glycoprotein. Overall, 114 out of the 809 women included in the study experienced complications during pregnancy, including miscarriage, preeclampsia/eclampsia, foetal death, and/or preterm birth. Women with complications had higher rates of antiphospholipid syndrome (40.5% vs 9.9%, p < 0.001) and higher rates of positivity for IgG anticardiolipin (33.9% vs 21.3%, p = 0.005), IgG anti-beta 2 glycoprotein (26.1% vs 14%, p = 0.007), and IgM anti-beta 2 glycoprotein (26.1% vs 16%, p = 0.032) antibodies, although no differences were found regarding lupus anticoagulant. Among the treatments received, only heparin was more commonly used by women with pregnancy complications. We did not find differences in corticosteroid or hydroxychloroquine use. CONCLUSIONS: The likelihood of term pregnancy is higher before the diagnosis of SLE. In our cohort, positivity for anticardiolipin IgG and anti-beta-2- glycoprotein IgG/IgM, but not lupus anticoagulant, was associated with a higher risk of poorer pregnancy outcomes.
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Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Complicações na Gravidez , Nascimento Prematuro , Reumatologia , Gravidez , Humanos , Recém-Nascido , Feminino , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Síndrome Antifosfolipídica/complicações , Complicações na Gravidez/epidemiologia , Estudos Retrospectivos , beta 2-Glicoproteína I , Anticoagulantes , Imunoglobulina G , Imunoglobulina MRESUMO
OBJECTIVES: The potential relationship between diffuse idiopathic skeletal hyperostosis (DISH) and bone microstructure has not been studied in women. We aimed to assess the association between the trabecular bone score (TBS) and DISH in postmenopausal women, as well as the role of other parameters related to bone metabolism, such as bone mineral density (BMD), calciotropic hormones, and bone remodeling markers. METHODS: Cross-sectional study, nested in a prospective population-based cohort (Camargo cohort). Clinical covariates, DISH, TBS, vitamin D, parathormone, BMD and serum bone turnover markers, were analyzed. RESULTS: We have included 1545 postmenopausal women (mean age, 62±9 years). Those with DISH (n = 152; 8.2%) were older and had a significantly higher prevalence of obesity, metabolic syndrome, hypertension, and type 2 diabetes mellitus (p<0.05). Moreover, they had lower TBS values (p = 0.0001) despite having a higher lumbar spine BMD (p<0.0001) and a higher prevalence of vertebral fractures than women without DISH (28.6% vs. 15.1%; p = 0.002). When analyzing DISH through Schlapbach grades, women without DISH had a median TBS value consistent with a normal trabecular structure while the values for women with DISH from grades 1 to 3 were consistent with a partially degraded trabecular structure. Women with vertebral fractures and DISH had a mean TBS corresponding to a degraded trabecular structure (1.219±0.1). After adjusting for confounders, the estimated TBS means were 1.272 (1.253-1.290) in the DISH group, and 1.334 (1.328-1.339) in the NDISH group (p<0.0001). CONCLUSION: An association between DISH and TBS has been shown in postmenopausal women, in which hyperostosis has been significantly and consistently related to trabecular degradation and, therefore, to deterioration in bone quality after adjusting for confounding variables.
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Diabetes Mellitus Tipo 2 , Hiperostose Esquelética Difusa Idiopática , Fraturas da Coluna Vertebral , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Absorciometria de Fóton , Osso Esponjoso/diagnóstico por imagem , Estudos Prospectivos , Hiperostose Esquelética Difusa Idiopática/diagnóstico por imagem , Hiperostose Esquelética Difusa Idiopática/epidemiologia , Estudos Transversais , Pós-Menopausa , Densidade Óssea , Vitamina D , Vértebras Lombares/diagnóstico por imagemRESUMO
INTRODUCTION/OBJECTIVES: DISH has traditionally been considered a non-inflammatory rheumatic disorder. Currently, an inflammatory component has been theorized in the early phases of this condition (EDISH). The study is aimed at investigating a possible relationship between EDISH and chronic inflammation. METHOD: Analytical-observational study: participants from the Camargo Cohort Study were enrolled. We collected clinical, radiological, and laboratory data. C-reactive protein (CRP), albumin-to-globulin ratio (AGR), and triglyceride-glucose (TyG) index were assessed. EDISH was defined by Schlapbach's scale grades I or II. A fuzzy matching with tolerance factor = 0.2 was performed. Subjects without ossification (NDISH), sex- and age-matched with cases (1:4), acted as controls. Definite DISH was an exclusion criterion. Multivariable analyses were performed. RESULTS: We evaluated 987 persons (mean age 64 ± 8 years; 191 cases with 63.9% women). EDISH subjects presented more frequently obesity, T2DM, MetS, and the lipid pattern [↑TG ↓TC]. TyG index and alkaline phosphatase (ALP) were higher. Trabecular bone score (TBS) was significantly lower (1.310 [0.2] vs. 1.342 [0.1]; p = 0.025). CRP and ALP showed the highest correlation (r = 0.510; p = 0.0001) at lowest TBS level. AGR was lower, and its correlations with ALP (r = - 0.219; p = 0.0001) and CTX (r = - 0.153; p = 0.022), were weaker or non-significant in NDISH. After adjustment for potential confounders, estimated CRP means for EDISH and NDISH were 0.52 (95% CI: 0.43-0.62) and 0.41 (95% CI: 0.36-0.46), respectively (p = 0.038). CONCLUSIONS: EDISH was associated with chronic inflammation. Findings revealed an interplay between inflammation, trabecular impairment, and the onset of ossification. Lipid alterations were similar to those observed in chronic-inflammatory diseases. Key Points ⢠An inflammatory component has been theorized in early stages of DISH (EDISH) ⢠In EDISH group compared to non-DISH, we observed significantly higher correlations between biomarkers and some relevant variables. In particular, with alkaline phosphatase (ALP) and with trabecular bone score (TBS) ⢠EDISH has shown to be associated with chronic inflammation ⢠The lipid alterations observed in the EDISH group were similar to those observed in chronic-inflammatory diseases.
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Hiperostose Esquelética Difusa Idiopática , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Hiperostose Esquelética Difusa Idiopática/diagnóstico por imagem , Hiperostose Esquelética Difusa Idiopática/complicações , Estudos de Coortes , Fosfatase Alcalina , Inflamação/complicações , LipídeosRESUMO
OBJECTIVES: Autoantibodies and, specifically antinuclear antibodies (ANA), are the hallmark of systemic autoimmune diseases (AID). In the last decades, there has been great technical development to detect these autoantibodies along with an increased request for this test by clinicians, while the overall pre-test probability has decreased. In this study, we compare the diagnostic performance of three different methods for ANA screening (indirect immunofluorescence [IIF], addressable laser bead immunoassay [ALBIA], and fluorescence enzyme immunoassay [FEIA]). METHODS: Serum samples at baseline visit from 2,997 participants from the Camargo Cohort, a population with an overall low pre-test probability for systemic AID, were analyzed with the three methods. Participants have a minimum follow-up of 10 years and the development of autoimmune diseases was collected from clinical records. RESULTS: The highest frequency of positive ANA was observed by IIF assay. However, ALBIA showed high sensitivity for AID. Likewise, solid phase assays (SPA) presented higher specificity than IIF for AID. ANA prevalence with any method was significantly higher in females and overall increased with age. Triple positivity for ANA was significantly related to the presence of anti-dsDNA-SSA/Ro60, Ro52, SSB/La, RNP, Scl-70, and centromere-specificities. No association was found for anti-Sm - RNP68, or ribosomal P - specificities. Noteworthy, triple positivity for ANA screening was associated with diagnosis of systemic AID both at baseline visit and follow-up. CONCLUSIONS: ANA detection by IIF may be better when the pre-test probability is high, whereas SPA techniques are more useful in populations with an overall low pre-test probability for systemic AID.
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Anticorpos Antinucleares , Doenças Autoimunes , Feminino , Humanos , Autoanticorpos , Doenças Autoimunes/diagnóstico , Técnica Indireta de Fluorescência para Anticorpo/métodos , Imunoensaio/métodosRESUMO
BACKGROUND: A significant proportion of patients with retinal vein occlusion (RVO) are antiphospholipid antibodies (aPL) carriers. Relapsing disease occurs in nearly 10 % of cases and the role of aPL has not been established. The adjusted global antiphospholipid syndrome score (aGAPSS) was developed to assess the risk of clinical events in aPL carriers and its role in the management of RVO patients is unknown. OBJECTIVE: To analyze the values of aGAPSS in a large cohort of patients with RVO and population-based controls, and to assess its usefulness to predict RVO relapses. METHODS: Case-control study of RVO patients and population-based controls of similar age and sex. We have assessed and compared the aPL profile and the aGAPSS score in patients with and without relapsing disease and controls. RESULTS: Four-hundred and seventy-two RVO patients and 346 controls were included. Fifty-seven RVO patients had antiphospholipid syndrome (RVO-APS). Of them, 75.4 % had a high-risk profile compared to 3 % in controls (p = 0.0001). The median aGAPSS values were 8 [7-13], 3 [1-4], and 3 [0-4], in RVO-APS, RVO no-APS, and controls. Nineteen patients had had a recurrence of RVO before inclusion and 8 during the follow-up. APS was more prevalent in relapsing patients. In the adjusted multivariable regression model, the best predictor for RVO recurrence during the follow-up was an aGAPSS score ≥6 (OR 5.5, CI95% 1.3-23.7; p = 0.023). CONCLUSIONS: In patients with RVO, once the control of vascular risk factors has been optimized, the aGAPSS might help to identify those at risk of relapsing disease.
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Síndrome Antifosfolipídica , Oclusão da Veia Retiniana , Humanos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Estudos de Casos e Controles , Oclusão da Veia Retiniana/diagnóstico , Medição de Risco , RecidivaRESUMO
OBJECTIVES: To analyze the prevalence, incidence, survival and contribution on mortality of major central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). METHODS: Patients fulfilling the SLE 1997 ACR classification criteria from the multicentre, retrospective RELESSER-TRANS (Spanish Society of Rheumatology Lupus Register) were included. Prevalence, incidence and survival rates of major CNS neuropsychiatric (NP)-SLE as a group and the individual NP manifestations cerebrovascular disease (CVD), seizure, psychosis, organic brain syndrome and transverse myelitis were calculated. Furthermore, the contribution of these manifestations on mortality was analysed in Cox regression models adjusted for confounders. RESULTS: A total of 3591 SLE patients were included. Of them, 412 (11.5%) developed a total of 522 major CNS NP-SLE manifestations. 61 patients (12%) with major CNS NP-SLE died. The annual mortality rate for patients with and without ever major CNS NP-SLE was 10.8% vs 3.8%, respectively. Individually, CVD (14%) and organic brain syndrome (15.5%) showed the highest mortality rates. The 10% mortality rate for patients with and without ever major CNS NP-SLE was reached after 12.3â¯vs 22.8 years, respectively. CVD (9.8 years) and organic brain syndrome (7.1 years) reached the 10% mortality rate earlier than other major CNS NP-SLE manifestations. Major CNS NP-SLE (HR 1.85, 1.29-2.67) and more specifically CVD (HR 2.17, 1.41-3.33) and organic brain syndrome (HR 2.11, 1.19-3.74) accounted as independent prognostic factors for poor survival. CONCLUSION: The presentation of major CNS NP-SLE during the disease course contributes to a higher mortality, which may differ depending on the individual NP manifestation. CVD and organic brain syndrome are associated with the highest mortality rates.
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Lúpus Eritematoso Sistêmico , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Reumatologia , Humanos , Estudos Retrospectivos , Lúpus Eritematoso Sistêmico/epidemiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/epidemiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Sistema Nervoso CentralRESUMO
This study aims to compare the demographic characteristics, clinical features, serology, and fetal-maternal outcomes between women with obstetric antiphospholipid syndrome (APS) and those with non-criteria (NC)-APS and seronegative (SN)-APS. Two-hundred and sixty-three women with APS obstetric morbidity ever pregnant were included. Of those, 66 met the APS classification criteria, 140 were NC-APS, and 57 were SN-APS. Patients with other autoimmune diseases were excluded. Adverse pregnancy outcomes (APO) included early pregnancy loss, fetal death, preeclampsia, abruptio placentae, and preterm birth. The mean age of the study group was 33.6 ± 5.3 years, and patients were followed up for 129.5 ± 81.9 months. In the NC-APS group, 31 (22.1%) did not fulfill clinical and serological criteria (Subgroup A), 49 (35%) did meet clinical but not serologic criteria (Subgroup B), and 60 (42.9%) fulfilled the serologic criteria but not the clinical ones (Subgroup C). The cardiovascular risk burden was higher in the APS group, due to a higher proportion of smoking. Patients with criteria APS received more intensive treatment than patients in the other study groups. The addition of standard of care (SoC) treatment significantly improved live birth and decreased APO in all groups. Significant clinical differences were observed between the study groups. However, when treated with SoC, fetal-maternal outcomes were similar, with a significant improvement in live births and a decrease in APO. Risk stratification in patients with obstetric morbidity associated with APS can help individualize their treatment.
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Purpose: A high cardiovascular risk has been described in patients with rheumatoid arthritis (RA); the effects of different biological agents have also been described in these patients. The aim of the present study is to examine the effects of tumor necrosis factor inhibitors (TNFi) in the lipoprotein profile of RA patients using a broad laboratory assessment including a large number of non-routine tests. Patients and Methods: RA patients treated with and without TNFi (70 patients in each group) were cross-sectionally compared regarding a broad spectrum of lipoprotein parameters including serum levels of total and HDL, LDL and VLDL cholesterol triglycerides, lipoprotein A (LpA), apolipoprotein A1 (Apo A), B100 (Apo B) and paroxonase. For each lipoprotein subfraction (HDL, LDL and VLDL), we assess specific concentrations of cholesterol, triglycerides, phospholipids and proteins and total mass of each one. Additionally, HDL Apo A, LDL and VLDL Apo B concentrations and number of particles of LDL and VLDL were also determined. Exploratory univariate and multivariate analyses of the different variables were performed. Results: Seventy patients in each subset were enrolled. Patients on treatment with TNFi showed a trend to be younger and to have a longer disease duration. Regarding the lipoprotein analyses, borderline significant higher levels of serum Apo A were detected and an independent association with lower HDL mass, LDL triglyceride, VLDL cholesterol, VLDL Apo B, VLDL mass, number of VLDL cholesterol molecules and number of particles of VLDL was clearly observed. Conclusion: TNFi treatment was associated with beneficial atherogenic effects at the lipoprotein level especially centered in the VLDL-related parameters consistent with a reduction of the atherogenic risk.
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There is a strong need for biomarkers of rheumatoid arthritis (RA) in all phases of the patient's journey and to enable the implementation of precision medicine strategies to improve patient care. The objective of this study was to evaluate the presence of anti-protein-arginine deiminase (PAD) 4 IgG and IgA in the sera of RA patients and disease controls, and to investigate their association with joint erosion and biological treatment use. Sera from 104 RA and 155 controls were tested for the presence of anti-PAD4 IgG and IgA using a new particle-based multi-analyte technology (PMAT). Information on the erosive disease and biological treatment use was available for 54 of the RA patients, who were also tested for anti-citrullinated protein antibodies (ACPA). An association between the autoantibodies and these clinical features was investigated. Anti-PAD4 showed sensitivity and specificity values of 25.0% and 94.2% for IgG and of 21.2% and 94.8% for IgA for RA, respectively. The levels of these antibodies were also significantly higher in RA patients vs. controls, in erosive RA vs. non-erosive disease, and in patients under biologics vs. patients that were not on this treatment regimen. The anti-PAD4 IgG and IgA levels were correlated (rho = 0.60, p < 0.0001), but individuals that were positive for only one of the two isotypes were also observed. Anti-PAD4 IgG and IgA are associated with severe RA, and they represent valuable biomarkers for prognosis prediction and patient stratification.
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Systemic sclerosis (SSc) is an autoimmune disease that affects skin and multiple internal organs. TGF-ß, a central trigger of cutaneous fibrosis, activates fibroblasts with the involvement of the stress-inducible chaperone heat shock protein 90 isoform α (Hsp90α). Available evidence supports overexpression and secretion of Hsp90α as a feature in profibrotic pathological conditions. The aim of this work is to investigate the expression and function of Hsp90α in experimental models of skin fibrosis such as human fibroblasts, C57BL/6 mice, and in human SSc. For this purpose, we generated a new experimental model based on doxorubicin administration with improved characteristics with respect to the bleomycin model. We visualized disease progression in vivo by fluorescence imaging. In this work, we obtained Hsp90α mRNA overexpression in human skin fibroblasts, in bleomycin- and doxorubicin-induced mouse fibrotic skin, and in lungs of bleomycin- and doxorubicin-treated mice. Hsp90α-deficient mice showed significantly decreased skin thickness compared with wild-type mice in both animal models. In SSc patients, serum Hsp90α levels were increased in patients with lung involvement and in patients with the diffuse form of SSc (dSSc) compared with patients with the limited form of SSc. The serum Hsp90α levels of patients dSSc were correlated with the Rodnan score and the forced vital capacity variable. These results provide new supportive evidence of the contribution of the Hsp90α isoform in the development of skin fibrosis. In SSc, these results indicated that higher serum levels were associated with dSSc and lung fibrosis.
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Proteínas de Choque Térmico HSP90/metabolismo , Escleroderma Sistêmico , Dermatopatias , Animais , Bleomicina , Modelos Animais de Doenças , Doxorrubicina/metabolismo , Fibroblastos , Fibrose , Proteínas de Choque Térmico/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Escleroderma Sistêmico/metabolismo , Pele , Dermatopatias/patologiaRESUMO
BACKGROUND: Glucocorticoids have been suggested as a potential therapy in refractory obstetric antiphospholipid syndrome (oAPS). Our aims were to describe a cohort of patients with oAPS treated with low-dose glucocorticoids and to perform a systematic review and meta-analysis evaluating the effects of additional glucocorticoids on the pregnancy outcomes in oAPS patients. METHODS: Retrospective study that included 11 women diagnosed with primary antiphospholipid syndrome. The meta-analysis was conducted by fitting random effects models and was checked for heterogeneity. RESULTS: All women had suffered from early pregnancy losses and two also had a history of fetal deaths. We studied 47 pregnancies that resulted in 32 abortions (68.1%) and 3 fetal deaths (6.4%). Twenty-six pregnancies were under treatment, mainly LDA and LMWH. Low-dose glucocorticoids were indicated in 13 pregnancies (always in association with LDA and LMWH). There was a decrease in pregnancy loss in those patients treated with LDA and LMWH. Treatment with glucocorticoids significantly increased the rate of successful pregnancy (38.5% abortions in treated vs 85.3% abortions in non-treated pregnancies; p=0.003). After multivariate GEE analysis, only glucocorticoids remained inversely associated with pregnancy loss (OR=0.157, (CI 0.025-0.968, p=0.046)). The meta-analysis showed that glucocorticoids tended to improve the frequency of successful pregnancy (OR= 0.509 (0.252-1.028), p=0.06). Three cases of gestational diabetes and one of preeclampsia were observed in our cohort. The meta-analysis, which mostly included studies using high-dose steroids, showed that glucocorticoids increased not only the frequency of preeclampsia and gestational diabetes, but also the rate of pre-term birth. CONCLUSIONS: The efficacy of low-dose glucocorticoids in addition to the standard therapy in patients with refractory oAPS should be confirmed in well-designed clinical trials. However, high doses of steroids significantly increase the frequency of maternal and fetal morbidities, making their use strongly inadvisable.
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Aborto Espontâneo , Síndrome Antifosfolipídica , Diabetes Gestacional , Lúpus Eritematoso Sistêmico , Pré-Eclâmpsia , Complicações na Gravidez , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia , Síndrome Antifosfolipídica/complicações , Estudos de Coortes , Feminino , Morte Fetal , Glucocorticoides/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Lúpus Eritematoso Sistêmico/complicações , Prednisona/uso terapêutico , Gravidez , Complicações na Gravidez/tratamento farmacológico , Resultado da Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVE: To characterize the demographic, genetic, clinical, and serological features of patients with anti-3hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune-mediated necrotizing myopathy (IMNM) in a region of northern Spain. METHODS: Study of all patients diagnosed with anti-HMGCR IMNM during a 5-year period at a reference hospital in northern Spain. Besides clinical and laboratory data, we analyzed the genetic influence of HLA genes and the rs4149056 (c.521T>C) single nucleotide polymorphism (SNP) in the SLCO1B1 gene. RESULTS: 8 patients (5 women, 3 men) with a mean ± SD age of 64.9 ± 7.3 years, fulfilled the criteria for anti-HMGCR IMNM. The incidence rate was 0.6 per 100.000 person-years and the prevalence 3 per 100.000 population. All patients had been exposed to statins. All of them had predominant lower limb proximal and symmetric muscle weakness that was severe in 2 and had elevated serum CK levels with a median [IQR] of 4488 [2538-9194] IU/L. Serum 25hydroxy vitamin D levels were decreased in all patients in whom it was determined. The 3 patients with a previous diagnosis of hypothyroidism had abnormal levels of TSH at the time of diagnosis. All patients experienced improvement with different schemes of immunosuppressive therapy. Noteworthy, 7 of 8 patients carried the HLA-DRB1*11 allele. The frequency of the rs4149056 C allele in the SLCO1B1 gene (12.5%) was similar to that of the general population. CONCLUSION: In northern Spain, anti-HMGCR IMNM preferentially affects people over 50 years of age who are carriers of the HLA-DRB1*11 allele and take statins. Both low vitamin D levels and hypothyroidism may play a potential predisposing role in the development of this disease.
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Doenças Autoimunes , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipotireoidismo , Doenças Musculares , Miosite , Idoso , Autoanticorpos , Feminino , Cadeias HLA-DRB1 , Humanos , Hidroximetilglutaril-CoA Redutases , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Transportador 1 de Ânion Orgânico Específico do Fígado , Masculino , Pessoa de Meia-Idade , Músculo Esquelético , Doenças Musculares/epidemiologia , Doenças Musculares/genética , Miosite/epidemiologia , Miosite/genética , Necrose , Vitamina DRESUMO
OBJECTIVE: To analyse a cohort of pregnant patients with systemic lupus erythematosus and compare the outcomes of both the disease and pregnancy with the results of previous studies conducted in the same geographical area. PATIENTS AND METHODS: Retrospective cohort study of 37 women with systemic lupus erythematosus (64 pregnancies) followed in a multidisciplinary unit. Comparative study with similar Spanish studies identified after literature search. RESULTS: Our cohort was characterized by an older age and by the presence of non-Caucasian patients. Although we found no clinical differences, from the serological point of view our cohort presented a higher frequency of antiphospholipid antibodies. Patients included in this study were treated more frequently with antimalarials and low-dose aspirin. Systemic lupus erythematosus flare frequency was very similar between the different studies, and we did not identify clear predictors for them. Although the rate of live births was similar among studies, the obstetric outcome of our series was better with a very low rate of preeclampsia, preterm birth and low birth weight newborn. The only predictor of adverse obstetric event was age. CONCLUSIONS: Although changes in the therapeutic attitude and planning of pregnancy in recent years have not had a direct impact on the rate of systemic lupus erythematosus flares during pregnancy, they have meant an improvement in the obstetric results. The introduction of new variables independent of the disease such as age at conception, socio-cultural origin, or the availability of multidisciplinary units should be considered in the results of future studies.
Assuntos
Lúpus Eritematoso Sistêmico , Complicações na Gravidez , Nascimento Prematuro , Idoso , Feminino , Humanos , Recém-Nascido , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Gravidez , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , Espanha/epidemiologiaRESUMO
The adjusted Global Antiphospholipid Syndrome (APS) Score (aGAPSS) is a tool proposed to quantify the risk for antiphospholipid antibody (aPL)-related clinical manifestations. However, aGAPSS has been validated mainly for thrombotic events and studies on APS-related obstetric manifestations are scarce. Furthermore, the majority of them included patients with positive aPL and different autoimmune diseases. Here, we assess the utility of aGAPSS to predict the response to treatment in aPL carriers without other autoimmune disorders. One-hundred and thirty-seven women with aPL ever pregnant were included. Sixty-five meet the APS classification criteria, 61 had APS-related obstetric manifestations, and 11 were asymptomatic carriers. The patients' aGAPSS risk was grouped as low (< 6, N = 73), medium (6-11, N = 40), and high risk (≥ 12, N = 24). Since vascular risk factors included in the aGAPSS were infrequent in this population (< 10%), the aGAPSS score was mainly determined by the aPL profile. Overall, the live birth rate was 75%, and 37.2% of the patients had at least one adverse pregnancy outcome (APO). When considering patients according to the aGAPSS (high, medium, and low risk), no significant differences were found for pregnancy loss (29.2%, 25%, and 21.9%) or APO (33.3%, 47.5%, and 32.9%). In the present study, including aPL carriers without other autoimmune diseases, aGAPSS is not a valuable tool to identify patients at risk for obstetric complications despite treatment. In these patients with gestational desire, in addition to the aPL profile, other pregnancy-specific factors, such as age or previous obstetric history, should be considered.
Assuntos
Síndrome Antifosfolipídica , Doenças Autoimunes , Trombose , Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Doenças Autoimunes/complicações , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Trombose/etiologiaRESUMO
The natural history of antiphospholipid antibodies (aPL) carriers is not well-established. The objectives of the present study were (a) to study the probability of developing clinical criteria of antiphospholipid syndrome (APS), (b) to identify potential risk factors for developing thrombosis and/or obstetric complications, (c) to study the association between the antibody profile and development of APS, and (d) to determine the efficacy of primary prophylaxis. We retrospectively analyzed 138 subjects with positive aPL who did not fulfill clinical criteria for APS. The mean follow-up time was 138 ± 63.0 months. Thirteen patients (9.4%) developed thrombosis after an average period of 73.0 ± 48.0 months. Independent risk factors for thrombosis were smoking, hypertension, thrombocytopenia, and triple aPL positivity. Low-dose acetyl salicylic acid did not prevent thrombotic events. A total of 28 obstetric complications were detected in 92 pregnancies. During the follow-up, only two women developed obstetric APS. Prophylactic treatment in pregnant women was associated with a better outcome in the prevention of early abortions. The thrombosis rate in patients with positive aPL who do not meet diagnostic criteria for APS is 0.82/100 patients-year. Smoking, hypertension, thrombocytopenia, and the aPL profile are independent risk factors for the development of thrombosis in aPL carriers. Although the incidence of obstetric complications in this population is high (31.6%), only a few of them meet APS criteria. In these women, prophylactic treatment might be effective in preventing early abortions.
Assuntos
Síndrome Antifosfolipídica , Hipertensão , Trombocitopenia , Trombose , Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Gravidez , Estudos Retrospectivos , Fatores de Risco , Trombose/epidemiologia , Trombose/etiologiaRESUMO
BACKGROUND: The role of vitamin D status in COVID-19 patients is a matter of debate. OBJECTIVES: To assess serum 25-hydroxyvitamin D (25OHD) levels in hospitalized patients with COVID-19 and to analyze the possible influence of vitamin D status on disease severity. METHODS: Retrospective case-control study of 216 COVID-19 patients and 197 population-based controls. Serum 25OHD levels were measured in both groups. The association of serum 25OHD levels with COVID-19 severity (admission to the intensive care unit, requirements for mechanical ventilation, or mortality) was also evaluated. RESULTS: Of the 216 patients, 19 were on vitamin D supplements and were analyzed separately. In COVID-19 patients, meanâ ±â standard deviation 25OHD levels were 13.8â ±â 7.2 ng/mL, compared with 20.9â ±â 7.4 ng/mL in controls (Pâ <â .0001). 25OHD values were lower in men than in women. Vitamin D deficiency was found in 82.2% of COVID-19 cases and 47.2% of population-based controls (Pâ <â .0001). 25OHD inversely correlates with serum ferritin (Pâ =â .013) and D-dimer levels (Pâ =â .027). Vitamin D-deficient COVID-19 patients had a greater prevalence of hypertension and cardiovascular diseases, raised serum ferritin and troponin levels, as well as a longer length of hospital stay than those with serum 25OHD levels ≥20 ng/mL. No causal relationship was found between vitamin D deficiency and COVID-19 severity as a combined endpoint or as its separate components. CONCLUSIONS: 25OHD levels are lower in hospitalized COVID-19 patients than in population-based controls and these patients had a higher prevalence of deficiency. We did not find any relationship between vitamin D concentrations or vitamin deficiency and the severity of the disease.