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OBJECTIVE: To investigate the risk of DM and evaluate the impact of SLE therapies on the risk of developing DM in patients with SLE. METHODS: Electronic database searches of PubMed, Embase, Cochrane Library and Web of Science were performed from inception to February 2023. Cohort and cross-sectional studies that analysed the risk of DM in patients with SLE were included. The associations between diabetes and antirheumatic agents, such as antimalarials and glucocorticoids, were analysed in cohort studies. Data were pooled using fixed- or random-effects meta-analysis to estimate pooled odd ratios (OR), relative risks (RR) and 95% confidence intervals (CIs). This study was registered with PROSPERO (CRD42023402774). RESULTS: A total of 37 studies (23 cross-sectional and 14 cohort studies) involving 266 537 patients with SLE were included. The pooled analyses from cross-sectional studies and cohort studies did not show an increased risk of DM in SLE patients (OR = 1.05, 95% CI 0.87-1.27; P = 0.63 and RR = 1.32, 95% CI 0.93-1.87; P = 0.12, respectively). However, several cohort studies consistently demonstrated a reduced risk of diabetes with antimalarials, while glucocorticoid use has been associated with an increased risk of developing diabetes. Age, sex, hypertension and immunosuppressants have not been identified as risk factors for DM in SLE patients. CONCLUSION: Although there was no increased risk of DM in patients with SLE compared with controls, HCQ users or adherents had a decreased risk, whereas glucocorticoid users had an increased risk.
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Antimaláricos , Diabetes Mellitus , Glucocorticoides , Lupus Eritematoso Sistémico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Humanos , Diabetes Mellitus/epidemiología , Glucocorticoides/uso terapéutico , Glucocorticoides/efectos adversos , Antimaláricos/uso terapéutico , Antimaláricos/efectos adversos , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Factores de Riesgo , Estudios TransversalesRESUMEN
INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease that often requires hospitalization. Most hospitalizations are due to infections and/or disease activity, for which several risk factors have been described in non-Mestizo patients. OBJECTIVE: To identify risk factors for hospitalization in patients with systemic lupus erythematosus (SLE). METHODS: This was an observational case-control study of patients with SLE in San Luis Potosí, Mexico, evaluated from January 2019 to October 2020. We compared hospitalized lupus patients with non-hospitalized lupus patients. We used descriptive statistics and logistic regression to describe potential risk factors. RESULTS: Of a total of 202 patients, 89 (45.1%) were hospitalized; these patients were younger, had shorter disease duration, higher disease activity scores (systemic lupus erythematosus disease activity index-SLEDAI), and more accumulated damage than non-hospitalized patients. The primary reasons for hospitalization were disease activity (60.7%), kidney disease, infection, and drug toxicity (5.6%). Multivariate analysis revealed several risk factors associated with hospitalization, including elevated creatinine, C-reactive protein, neutrophil levels, and constitutional symptoms, while prolonged international normalized ratio (INR), longer stay in the intensive care unit (ICU), and vasopressor use were associated with mortality. The use of antimalarials was a protective factor against hospitalization. Survival analysis revealed that patients with hospital-acquired infections had a lower probability of survival. CONCLUSIONS: Disease activity was the most common reason for hospitalization; kidney, constitutional, and hematological factors were associated with hospitalization; and the use of antimalarial was a protective factor for hospitalization.
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Hospitalización , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , México/epidemiología , Femenino , Hospitalización/estadística & datos numéricos , Factores de Riesgo , Adulto , Masculino , Estudios de Casos y Controles , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto Joven , Antimaláricos/uso terapéutico , Modelos Logísticos , Tiempo de Internación/estadística & datos numéricosRESUMEN
BACKGROUND: Hospitalizations due to systemic lupus erythematosus (SLE) incur substantial resource use. Hospitalization trends provide a key benchmark of the disease burden. However, there is little long-term data in Mexico. Therefore, we evaluated Mexican hospitalization trends for SLE during 2000-2019. METHODS: Hospitalization trends of SLE were studied using data from 2000 to 2019 releases of the National Dynamic Cubes of the General Direction of Health Information, which provides data on hospitalization discharges in Mexico. Patients aged ≥15 years hospitalized during the study period with a principal discharge diagnosis of SLE (ICD-10 code M32) were included. RESULTS: From 2000 to 2019, there were 17,081 hospitalizations for SLE, of which 87.6% were in females and 87% in subjects aged 15-44 years. From 2000 to 2019, the age-standardized hospitalization rate for patients with SLE increased from 0.38 per 100,000 persons to 0.65 per 100,000 persons with an average annual percentage change (APC) of 2.9% (95% CI 6.2-63.2). Although there was a significant uptrend from 2000 through 2011, there was a significant decline from 2011 to 2019 (APC: -4.8%, 95% CI -7.0% to -2.5%). Similar trends were identified in subjects aged 15-44 years and in both sexes. The length of stay and inpatient mortality decreased between 2000-2009 and 2010-2019. CONCLUSIONS: Although there was a substantial increase in SLE hospitalizations in 2000-2019, in 2011-2019, a decreased trend was reported in younger patients and in females and males. The length of stay was also reduced.
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Lupus Eritematoso Sistémico , Humanos , Masculino , Femenino , Lupus Eritematoso Sistémico/epidemiología , México/epidemiología , HospitalizaciónRESUMEN
INTRODUCTION: Lupus nephritis requires antinuclear antibodies as classification criteria. There is a group of patients with nephrotic syndrome and conclusive histopathological findings for lupus nephritis, without classification criteria for systemic lupus erythematosus (SLE) or extrarenal manifestations. These groups of patients have been described as "lupus-like" nephritis or "renal-limited lupus nephritis". METHODS: Renal biopsy with histopathological evaluation with "full-house" immune-reactants in patients with negative antinuclear antibodies. RESULTS: We report four cases with nephrotic syndrome and one with hematuria-proteinuria syndrome: two with impaired glomerular filtration rate and three with preserved renal function; urinary sediment with hematuria without dysmorphia and without extrarenal manifestations for autoimmune disease, negative antinuclear antibodies (ANA) and anti-double stranded DNA (anti-dsDNA); normal C3 and C4 complement levels. Renal biopsy in all cases was consistent for lupus nephritis class V. All patients received treatment as lupus nephritis protocol; only one case received induction with cyclophosphamide and methylprednisolone boluses, the rest received mycophenolic acid and prednisone as induction and maintenance. Two of the cases induced with mycophenolic acid relapsed, requiring cyclophosphamide for 6 months, achieving complete remission. All patients received renin-angiotensin-aldosterone system blockade and hydroxychloroquine. At follow-up, 4 cases still have negative antibodies and are without extrarenal manifestations for SLE classification criteria. The other case, during pregnancy several years after initial diagnosis, had preeclampsia with nephrotic proteinuria and a new determination of positive ANA and anti-dsDNA antibodies, complement levels below normal limits. CONCLUSION: The follow-up of patients with membranous glomerulopathy must be close; lupus like nephritis may be the first manifestation of the disease.
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Glomerulonefritis Membranosa , Nefritis Lúpica , Anticuerpos Antinucleares , Proteínas del Sistema Complemento , Ciclofosfamida , Femenino , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/tratamiento farmacológico , Hematuria , Hospitales , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/tratamiento farmacológico , México , Ácido Micofenólico , Embarazo , ProteinuriaRESUMEN
Introduction: After more than 20 years of sustained work, the Latin American Group for the Study of Lupus (GLADEL) has made a significant number of contributions to the field of lupus, not only in the differential role that race/ethnicity plays in its course and outcome but also in several other studies including the beneficial effects of using antimalarials in lupus patients and the development of consensus guidelines for the treatment of lupus in our region. Methods: A new generation of "Lupus Investigators" in more than 40 centers throughout Latin America has been constituted in order to continue the legacy of the investigators of the original cohort and to launch a novel study of serum and urinary biomarkers in patients with systemic lupus erythematosus. Results: So far, we have recruited 807 patients and 631 controls from 42 Latin-American centers including 339 patients with SLE without renal involvement, 202 patients with SLE with prevalent but inactive renal disease, 176 patients with prevalent and active renal disease and 90 patients with incident lupus nephritis. Conclusions: The different methodological aspects of the GLADEL 2.0 cohort are discussed in this manuscript, including the challenges and difficulties of conducting such an ambitious project.
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OBJECTIVES: This ongoing Phase-2, randomised, placebo-controlled, double-blind study evaluated the efficacy, safety and pharmacokinetics of intravenous belimumab in childhood-onset systemic lupus erythematosus (cSLE). METHODS: Patients (5 to 17 years) were randomised to belimumab 10 mg/kg intravenous or placebo every 4 weeks, plus standard SLE therapy. Primary endpoint: SLE Responder Index (SRI4) response rate (Week 52). Key major secondary endpoints: proportion of patients achieving the Paediatric Rheumatology International Trials Organisation/American College of Rheumatology (PRINTO/ACR) response using 50 and '30 alternative' definitions (Week 52), and sustained response (Weeks 44 to 52) by SRI4 and Parent Global Assessment of well-being (Parent-global). Safety and pharmacokinetics were assessed. Study not powered for statistical testing. RESULTS: Ninety-three patients were randomised (belimumab, n=53; placebo, n=40). At Week 52, there were numerically more SRI4 responders with belimumab versus placebo (52.8% vs 43.6%; OR 1.49 (95% CI 0.64 to 3.46)). PRINTO/ACR 30 alternative (52.8% vs 27.5%; OR 2.92 (95% CI 1.19 to 7.17)) and PRINTO/ACR 50 (60.4% vs 35.0%; OR 2.74 (95% CI 1.15 to 6.54)) responses were more frequent with belimumab than placebo, as were sustained responses for SRI4 (belimumab, 43.4%; placebo, 41.0%; OR 1.08 (95% CI 0.46 to 2.52)) and Parent-global (belimumab, 59.1%; placebo, 33.3%; OR 3.49 (95% CI 1.23 to 9.91)). Serious adverse events were reported in 17.0% of belimumab patients and 35.0% of placebo patients; one death occurred (placebo). Week-52, geometric mean (95% CI) belimumab trough concentration was 56.2 (45.2 to 69.8) µg/mL. CONCLUSION: The belimumab intravenous pharmacokinetics and benefit-risk profile in cSLE are consistent with adult belimumab studies and the 10 mg/kg every 4 weeks dose is appropriate. TRIAL REGISTRATION NUMBER: NCT01649765.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Administración Intravenosa , Adolescente , Factor Activador de Células B/antagonistas & inhibidores , Niño , Preescolar , Método Doble Ciego , Femenino , Humanos , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND: Mycophenolic acid (MPA) is an effective oral immunosuppressive drug used to treat lupus nephritis (LN), which exhibits large pharmacokinetic variability. This study aimed to characterize MPA pharmacokinetic behaviour in Mexican LN patients and to develop a population pharmacokinetic model which identified factors that influence MPA pharmacokinetic variability. METHODS: Blood samples from LN patients treated with mycophenolate mofetil (MMF) were collected pre dose and up to six hours post dose. MPA concentrations were determined by a validated ultra-performance liquid chromatography tandem mass spectrometry technique. Patients were genotyped for polymorphisms in enzymes (UGT1A8, 1A9 and 2B7) and transporters (ABCC2 and SLCO1B3). The anthropometric, clinical, genetic and co-medication characteristics of each patient were considered as potential covariates to explain the variability. RESULTS: A total of 294 MPA concentrations from 40 LN patients were included in the development of the model. The data were analysed using NONMEM software and were best described by a two-compartment linear model. MPA CL, Vc, Vp, Ka and Q were 15.4 L/h, 22.86 L, 768 L, 1.28 h-1 and 20.3 L/h, respectively. Creatinine clearance and prednisone co-administration proved to have influence on clearance, while body weight influenced Vc. The model was internally validated, proving to be stable. MMF dosing guidelines were obtained through stochastic simulations performed with the final model. CONCLUSIONS: This is the first MPA population pharmacokinetic model to have found that co-administration of prednisone results in a considerable increase on clearance. Therefore, this and the other covariates should be taken into account when prescribing MMF in order to optimize the immunosuppressant therapy in patients with LN.
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Inmunosupresores/farmacocinética , Nefritis Lúpica/tratamiento farmacológico , Modelos Biológicos , Ácido Micofenólico/farmacocinética , Prednisona/farmacocinética , Adolescente , Adulto , Quimioterapia Combinada , Femenino , Humanos , Inmunosupresores/administración & dosificación , Modelos Lineales , Nefritis Lúpica/sangre , Masculino , México , Persona de Mediana Edad , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Ácido Micofenólico/administración & dosificación , Prednisona/administración & dosificación , Programas Informáticos , Adulto JovenRESUMEN
Filifactor alocis and Dialister pneumosintes have been associated with the initiation and progression of periodontitis (PE). We determined and compared the frequency of both bacteria in patients with PE, rheumatoid arthritis (RA), and PE/RA simultaneously. Detection was performed by polymerase chain reaction in the subgingival biofilm. Bacteria were more frequent in patients with PE, and clinical periodontal parameters such as pocket depth (PD) and clinical attachment loss (CAL) were significantly higher in patients with PE/RA. F. alocis and D. pneumosintes could influence PD and CAL, hence participating in the initiation and progression of PE in patients with RA.
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Artritis Reumatoide/microbiología , Clostridiales/patogenicidad , Periodontitis/microbiología , Veillonellaceae/patogenicidad , Adulto , Artritis Reumatoide/tratamiento farmacológico , Biopelículas , Humanos , México , Persona de Mediana Edad , Periodontitis/tratamiento farmacológicoRESUMEN
OBJECTIVE: This report aims to determine the safety, pharmacokinetics (PK) and efficacy of subcutaneous golimumab in active polyarticular-course juvenile idiopathic arthritis (polyJIA). METHODS: In this three-part randomised double-blinded placebo-controlled withdrawal trial, all patients received open-label golimumab (30 mg/m2 of body surface area; maximum: 50 mg/dose) every 4 weeks together with weekly methotrexate during Part 1 (weeks 0-16). Patients with at least 30% improvement per American College of Rheumatology Criteria for JIA (JIA ACR30) in Part 1 entered the double-blinded Part 2 (weeks 16-48) after 1:1 randomisation to continue golimumab or start placebo. In Part 3, golimumab was continued or could be restarted as in Part 1. The primary outcome was JIA flares in Part 2; secondary outcomes included JIA ACR50/70/90 responses, clinical remission, PK and safety. RESULTS: Among 173 patients with polyJIA enrolled, 89.0% (154/173) had a JIA ACR30 response and 79.2%/65.9%/36.4% demonstrated JIA ACR50/70/90 responses in Part 1. At week 48, the primary endpoint was not met as treatment groups had comparable JIA flare rates (golimumab vs placebo: 32/78=41% vs 36/76=47%; p=0.41), and rates of clinical remission were comparable (golimumab vs placebo: 10/78=12.8% vs 9/76=11.8%). Adverse event and serious adverse event rates were similar in the treatment groups during Part 2. Injection site reactions occurred with <1% of all injections. PK analysis confirmed adequate golimumab dosing for polyJIA. CONCLUSION: Although the primary endpoint was not met, golimumab resulted in rapid, clinically meaningful, improvement in children with active polyJIA. Golimumab was well tolerated, and no unexpected safety events occurred. CLINICAL TRIAL REGISTRATION: NCT01230827; Results.
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Anticuerpos Monoclonales/administración & dosificación , Antirreumáticos/administración & dosificación , Artritis Juvenil/tratamiento farmacológico , Artritis/tratamiento farmacológico , Metotrexato/administración & dosificación , Adolescente , Artritis/patología , Artritis Juvenil/patología , Niño , Preescolar , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Inducción de Remisión , Brote de los Síntomas , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine and compare the distribution of Porphyromonas gingivalis fimA genotypes in patients affected by Rheumatoid arthritis (RA) and periodontitis (PE). MATERIALS AND METHODS: This study involved 394 subjects divided into four groups, RA, PE, RA and PE and healthy subjects. PE was diagnosed by using clinical attachment loss (CAL) and probing depth (PD) indexes. Presence of P. gingivalis and its genotypes was identified by polymerase chain reaction in subgingival biofilm. RESULTS: P. gingivalis was more frequent in patients with RA (82.69%), and fimA II genotype was the most frequent in all groups, especially in PE/RA (76.71%). There was statistical difference (p < .05) regarding the frequency of P. gingivalis genotypes such as fimA Ib, II and III. CONCLUSIONS: Distribution of P. gingivalis fimA II genotypes was different among groups, it could play a critical role in the presence of PE in RA patients.
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Artritis Reumatoide/genética , Infecciones por Bacteroidaceae/genética , Genotipo , Periodontitis/microbiología , Porphyromonas gingivalis/genética , Adulto , Artritis Reumatoide/microbiología , Infecciones por Bacteroidaceae/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Porphyromonas gingivalis/aislamiento & purificaciónRESUMEN
OBJECTIVES: To investigate the efficacy and safety of switching from infliximab reference product (RP) to its biosimilar or maintaining biosimilar treatment in patients with ankylosing spondylitis (AS). METHODS: This open-label extension study recruited patients with AS who completed a 54-week, randomised controlled study comparing CT-P13 with RP (PLANETAS). CT-P13 (5â mg/kg) was administered intravenously every 8â weeks from week 62 to week 102. Efficacy end points included the proportion of patients achieving Assessment of SpondyloArthritis international Society (ASAS)20. Antidrug antibodies (ADAs) were measured using an electrochemiluminescent method. Data were analysed for patients treated with CT-P13 in the main PLANETAS study and the extension (maintenance group) and those who were switched to CT-P13 during the extension study (switch group). RESULTS: Overall, 174 (82.9%) of 210 patients who completed the first 54â weeks of PLANETAS and agreed to participate in the extension were enrolled. Among these, 88 were maintained on CT-P13 and 86 were switched to CT-P13 from RP. In these maintenance and switch groups, respectively, ASAS20 response rates at week 102 were 80.7% and 76.9%. ASAS40 and ASAS partial remission were also similar between groups. ADA positivity rates were comparable (week 102: 23.3% vs 27.4%). Adverse events led to treatment discontinuation during the extension study in 3 (3.3%) and 4 (4.8%) patients, respectively. CONCLUSIONS: This is the first study to show that switching from RP to its biosimilar CT-P13 is possible without negative effects on safety or efficacy in patients with AS. In the maintenance group, CT-P13 was effective and well tolerated over 2â years of treatment. TRIAL REGISTRATION NUMBER: NCT01571206; Results.
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Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Sustitución de Medicamentos , Infliximab/uso terapéutico , Espondilitis Anquilosante/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anticuerpos/inmunología , Anticuerpos Monoclonales/inmunología , Antirreumáticos/inmunología , Biosimilares Farmacéuticos , Resistencia a Medicamentos/inmunología , Femenino , Humanos , Infliximab/inmunología , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: To assess the efficacy and safety of switching from the infliximab reference product (RP; Remicade) to its biosimilar CT-P13 (Remsima, Inflectra) or continuing CT-P13 in patients with rheumatoid arthritis (RA) for an additional six infusions. METHODS: This open-label extension study recruited patients with RA who had completed the 54-week, randomised, parallel-group study comparing CT-P13 with RP (PLANETRA; NCT01217086). CT-P13 (3â mg/kg) was administered intravenously every 8â weeks from weeks 62 to 102. All patients received concomitant methotrexate. Endpoints included American College of Rheumatology 20% (ACR20) response, ACR50, ACR70, immunogenicity and safety. Data were analysed for patients who received CT-P13 for 102â weeks (maintenance group) and for those who received RP for 54â weeks and then switched to CT-P13 (switch group). RESULTS: Overall, 302 of 455 patients who completed the PLANETRA study enrolled into the extension. Of these, 158 had received CT-P13 (maintenance group) and 144 RP (switch group). Response rates at week 102 for maintenance versus switch groups, respectively, were 71.7% vs 71.8% for ACR20, 48.0% vs 51.4% for ACR50 and 24.3% vs 26.1% for ACR70. The proportion of patients with antidrug antibodies was comparable between groups (week 102: 40.3% vs 44.8%, respectively). Treatment-emergent adverse events occurred in similar proportions of patients in the two groups during the extension study (53.5% and 53.8%, respectively). CONCLUSIONS: Comparable efficacy and tolerability were observed in patients who switched from RP to its biosimilar CT-P13 for an additional year and in those who had long-term CT-P13 treatment for 2â years. TRIAL REGISTRATION NUMBER: NCT01571219; Results.
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Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Sustitución de Medicamentos , Infliximab/uso terapéutico , Adolescente , Adulto , Anciano , Anticuerpos/inmunología , Anticuerpos Monoclonales/inmunología , Antirreumáticos/inmunología , Biosimilares Farmacéuticos , Quimioterapia Combinada , Femenino , Humanos , Infliximab/inmunología , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE OF REVIEW: The present paper establishes a narrative and analytical review of diffuse alveolar hemorrhage (DAH) in ANCA-associated vasculitis, systemic lupus erythematosus, and antiphospholipid syndrome. RECENT FINDINGS: Recent studies found a frequent association between DAH and infections and systemic lupus erythematosus and its associated factors. Biological therapies like rituximab have demonstrated benefit mainly in patients with ANCA-associated vasculitis. Main clinical manifestations of diffuse alveolar hemorrhage in these three diseases include dyspnea, pulmonary infiltrates, cough, and hypoxemia. The presence of hemorrhagic bronchoalveolar lavage, hemosiderin containing macrophages, or an increase of carbon monoxide diffusing capacity have been described in some series as helpful findings for the diagnosis. Hemoptysis has been seen mainly in systemic lupus erythematosus. The cornerstone of therapy includes glucocorticoids and cyclophosphamide, and recent findings in ANCA-associated vasculitis suggest the similar benefit of rituximab. Future evaluations and systematic reviews will help to define the real benefit for therapies that appeared to be controversial at the moment.
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Enfermedades Autoinmunes/complicaciones , Hemorragia/etiología , Enfermedades Pulmonares/etiología , Alveolos Pulmonares , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/mortalidad , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/mortalidad , Enfermedades Autoinmunes/mortalidad , Hemorragia/diagnóstico , Hemorragia/mortalidad , Hemorragia/terapia , Humanos , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/mortalidad , Enfermedades Pulmonares/terapia , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/mortalidad , Pronóstico , Factores de RiesgoRESUMEN
T regulatory (Treg) cells have a key role in the pathogenesis of chronic inflammatory and autoimmune diseases. A CD4+CD69+ T cell subset has been described that behaves as Treg lymphocytes, exerting an important immune suppressive effect. In this study, we analyzed the levels and function of CD4+CD69+ Treg cells in patients with systemic lupus erythematosus (SLE). Blood samples were obtained from 22 patients with SLE and 25 healthy subjects. Levels of CD4+CD69+ Treg cells were analyzed by multiparametric flow cytometry, and their function was measured by an assay of suppression of lymphocyte activation and through the inhibition of cytokine synthesis. We found an increased percent of CD4+CD25varCD69+TGF-ß+IL-10+Foxp3- lymphocytes in patients with SLE compared to controls. In addition, a significant diminution in the suppressive effect of these cells on the activation of autologous T lymphocytes was observed in most patients with SLE. Accordingly, CD69+ Treg cells from SLE patients showed a defective capability to inhibit the release of IL-2, IL-6, IL-10, and IL-17A by autologous lymphocytes. Our findings suggest that while CD4+CD69+ Treg lymphocyte levels are increased in SLE patients, these cells are apparently unable to contribute to the downmodulation of the autoimmune response and the tissue damage seen in this condition.
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Antígenos CD/inmunología , Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T/inmunología , Antígenos de Diferenciación de Linfocitos T/metabolismo , Lectinas Tipo C/inmunología , Lectinas Tipo C/metabolismo , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/metabolismo , Adolescente , Adulto , Femenino , Humanos , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-2/metabolismo , Interleucina-6/metabolismo , Masculino , Persona de Mediana Edad , Linfocitos T Reguladores/metabolismo , Adulto JovenRESUMEN
OBJECTIVE: Historically, it has been shown that rheumatoid arthritis (RA) and periodontitis (PE) share pathophysiological similarities and possibly a genetic background. In order to elucidate the genetic background between both diseases, we evaluated the distributions of five SNPs genotypes and all the possible haplotypes composed in subjects with isolated RA, PE, combined diseases and healthy controls. MATERIALS AND METHODS: The study population consisted of 280 Mexican subjects. Genomic DNA was isolated from buccal epithelial cells collected by cheek scrapings and analyzed for the determination of the following SNPs: IL-1α + 4845 (rs17561), IL-1α -889 (rs1800587), IL-1ß + 3954 (rs1143634), IL-1ß -511(rs16944) and TNF-α -308 (rs1800629). RESULTS: After adjustment for age, sex and smoking status, multiple logistic regression analysis revealed a no significant association in the genotype frequencies of TNF-α -308 and IL-1α + 4845 SNPs. Otherwise a significant association was observed in IL-1ß + 3954 and IL-1ß -511 (p < 0.05) while IL-1α -889 was of borderline statistical significance (p = 0.054). Also, we found three negative associated haplotypes with PE: IL-1α + 4845 G/IL-1ß -511 A, IL-1ß + 3954 C/IL-1ß -511 A and interestingly IL-1α -889 C/IL-1ß -511 A also with a positive association with RA. CONCLUSIONS: Some genotypes and haplotypes are associated with the diseases. But it seems that the genetic background of the association between RA and PE needs to be explored deeper.
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Artritis Reumatoide/genética , Citocinas/genética , Etnicidad/genética , Frecuencia de los Genes , Genotipo , Periodontitis/genética , Adulto , Alelos , Artritis Reumatoide/complicaciones , Femenino , Haplotipos , Humanos , Interleucina-1alfa/genética , Interleucina-1beta/genética , Masculino , México , Persona de Mediana Edad , Periodontitis/complicaciones , Polimorfismo Genético , Polimorfismo de Nucleótido Simple/genética , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a well-known but rare complication in patients (<1%) with systemic lupus erythematosus (SLE). However, current epidemiological data are quite scant. The aim of the present study was to describe potentially unrecognised risk factors. PATIENTS AND METHODS: We performed a multicentre, retrospective case-control study in Mexico between 1999 and 2014. We included a total of 168 patients who accounted for 77 episodes of PRES, as follows: SLE/PRES, 43 patients with 48 episodes; SLE without PRES, 96 patients; and PRES without SLE, 29 patients. SLE diagnosis was considered when patients fulfilled ≥4 American College of Rheumatology criteria. PRES was defined by reversible neurological manifestations and MRI changes. RESULTS: Patients with SLE/PRES were younger, presented with seizures as the most common manifestation (81%) and 18% had the typical occipital MRI finding. Hypertension (OR=16.3, 95% CI 4.03 to 65.8), renal dysfunction (OR=6.65, 95% CI 1.24 to 35.6), lymphopenia (OR=5.76, 95% CI 1.36 to 24.4), Systemic Lupus Erythematosus Activity Index ≥ 6 points (OR=1.11, 95% CI 1.01 to 1.22) and younger age (OR=0.86, 95% CI 0.81 to 0.91, p<0.001) were independent risk factors for development of PRES in SLE. Furthermore, dyslipidemia also characterised the association between PRES and SLE (OR=10.6, 95% CI 1.17 to 96.4). CONCLUSIONS: This is the largest reported series of patients with SLE and PRES. We were able to corroborate the known risk factors for of PRES, and found two previously undescribed factors (lymphopenia and dyslipidemia), which suggests that endothelial dysfunction is a key element in PRES pathogenesis in lupus patients.
Asunto(s)
Dislipidemias/epidemiología , Lupus Eritematoso Sistémico/epidemiología , Linfopenia/epidemiología , Síndrome de Leucoencefalopatía Posterior/epidemiología , Adulto , Estudios de Casos y Controles , Comorbilidad , Progresión de la Enfermedad , Femenino , Humanos , Masculino , México/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: To develop updated guidelines for the pharmacological management of rheumatoid arthritis (RA). METHODS: A group of experts representative of different geographical regions and various medical services catering to the Mexican population with RA was formed. Questions based on Population, Intervention, Comparison, and Outcome (PICO) were developed, deemed clinically relevant. These questions were answered based on the results of a recent systematic literature review (SLR), and the evidence's validity was assessed using the GRADE system, considered a standard for these purposes. Subsequently, the expert group reached consensus on the direction and strength of recommendations through a multi-stage voting process. RESULTS: The updated guidelines for RA treatment stratify various therapeutic options, including different classes of DMARDs (conventional, biologicals, and JAK inhibitors), as well as NSAIDs, glucocorticoids, and analgesics. By consensus, it establishes the use of these in different subpopulations of interest among RA patients and addresses aspects related to vaccination, COVID-19, surgery, pregnancy and lactation, and others. CONCLUSIONS: This update of the Mexican guidelines for the pharmacological treatment of RA provides reference points for evidence-based decision-making, recommending patient participation in joint decision-making to achieve the greatest benefit for our patients. It also establishes recommendations for managing a variety of relevant conditions affecting our patients.