RESUMEN
Background Cognitive impairment is frequent in systemic lupus erythematosus. Atrophy of the corpus callosum and hippocampus have been reported in patients with systemic lupus erythematosus, and diffusion tensor imaging studies have shown impaired white matter integrity, suggesting that white matter damage in systemic lupus erythematosus may underlie the cognitive impairment as well as other neuropsychiatric systemic lupus erythematosus manifestations. Retinal nerve fiber layer thickness, as assessed by optical coherence tomography, has been suggested as a biomarker for white matter damage in neurologic disorders such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. Retinal nerve fiber layer thinning may occur early, even in patients with mild clinical symptoms. Aim The objective of this study was to assess the association of retinal nerve fiber layer thickness, as a biomarker of white matter damage in systemic lupus erythematosus patients, with neuropsychiatric systemic lupus erythematosus manifestations, including cognitive impairment. Methods Twenty-one consecutive patients with systemic lupus erythematosus underwent neuropsychological testing using a validated computerized battery of tests as well as the Rey-Auditory verbal learning test. All 21 patients, as well as 11 healthy, age matched controls, underwent optical coherence tomography testing to assess retinal nerve fiber layer thickness. Correlations between retinal nerve fiber layer thickness and results in eight cognitive domains assessed by the computerized battery of tests as well as the Rey-Auditory verbal learning test were assessed in patients with systemic lupus erythematosus, with and without neuropsychiatric systemic lupus erythematosus, and compared to retinal nerve fiber layer thickness in healthy controls. Results No statistically significant correlation was found between retinal nerve fiber layer thickness in patients with systemic lupus erythematosus as compared to healthy controls. When evaluating by subgroups, no correlation was found between patients with or without neuropsychiatric systemic lupus erythematosus or cognitive impairment and retinal nerve fiber layer thickness. Conclusion Retinal nerve fiber layer thickness of systemic lupus erythematosus patients was not found to be statistically different compared to controls. Within systemic lupus erythematosus patients there was no correlation between retinal nerve fiber layer thickness and cognitive impairment or other neuropsychiatric systemic lupus erythematosus manifestations.
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Vasculitis por Lupus del Sistema Nervioso Central/patología , Fibras Nerviosas/patología , Nervio Óptico/patología , Adulto , Disfunción Cognitiva/patología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Coherencia ÓpticaRESUMEN
The American Academy of Ophthalmology published in 2011 revised recommendations regarding screening for hydroxychloroquine (HCQ) toxicity. We aimed to assess implementation of these recommendations by rheumatologists and ophthalmologists. A questionnaire regarding screening practices for HCQ toxicity was distributed among all members of the Israeli societies of Rheumatology and Ophthalmology. A total of 128 physicians responded to the questionnaire (rheumatologists: 60, ophthalmologists: 68). Only 5% of the rheumatologists and 15% of the ophthalmologists are aware of ophthalmologic assessments recommended for baseline and follow-up evaluation. When an abnormal test is detected, even if inappropriate for HCQ toxicity screening, 60% of the responders recommend cessation of therapy. Only 13% of the responders recommend first follow-up after five years for patients without risk factors; the remainder recommend more frequent testing. Ninety-six percent of the responders are not aware of all of the known risk factors for HCQ toxicity. Use of inappropriate tests to detect HCQ retinal toxicity may lead to unnecessary cessation of beneficial treatment with risk of disease flare, while lack of consideration of risk factors may put patients at risk for toxicity. These results emphasize the importance of implementing the recommendations to ensure safe and effective use of this drug.
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Antirreumáticos/toxicidad , Adhesión a Directriz/estadística & datos numéricos , Hidroxicloroquina/toxicidad , Tamizaje Masivo/normas , Enfermedades de la Retina/diagnóstico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Humanos , Hidroxicloroquina/uso terapéutico , Israel , Lupus Eritematoso Sistémico/tratamiento farmacológico , Oftalmólogos , Guías de Práctica Clínica como Asunto , Enfermedades de la Retina/inducido químicamente , Reumatólogos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
BACKGROUND: Memory impairment is prevalent in systemic lupus erythematosus (SLE); however, its pathogenesis is unknown. In a previous functional magnetic resonance imaging (fMRI) study we demonstrated altered brain activity dynamics and less brain deactivation in patients with SLE as compared with healthy controls, when performing a learning and memory task. Our findings localized this impairment to the default mode network (DMN), and particularly to its anterior medial prefrontal cortex node. In addition, altered networking of the hippocampal subsystem of the DMN was seen in patients with SLE when performing this task, as well as atrophy of the left hippocampus. The present study aimed to search for a structural substrate for the altered recruitment pattern observed in fMRI studies using diffusion tensor imaging (DTI). PATIENTS AND METHODS: Using DTI, we characterized brain diffusivity in 10 patients with SLE and nine healthy controls. Two tracts associated with the DMN were reconstructed: the corpus callosum (CC) and the cingulum bundle. The CC was segmented according to the Witelson segmentation scheme and the cingulum was segmented into superior and descending bundles. RESULTS: A significant increase in mean diffusivity (MD) was seen in patients with SLE without neuropsychiatric SLE (NPSLE) as compared with healthy controls in all five segments of the CC (segment 1: p = 0.043; segment 2: p = 0.005; segment 3: p = 0.003; segment 4: p = 0.012; segment 5: p = 0.023) as well as in the descending portion of the left cingulum bundle (p = 0.026). CONCLUSIONS: Increased MD values in the CC and the left cingulum may indicate impaired organization/reduced integrity of these tracts, which may underlie the abnormal pattern of brain activity recruitment of the DMN observed during a verbal learning and memory task. Taking into account the central role of the left hippocampus in verbal memory, the abnormal integrity of the left cingulum may contribute to the reduced performance of patients with SLE on verbal memory tasks.
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Cuerpo Calloso/diagnóstico por imagen , Giro del Cíngulo/diagnóstico por imagen , Lupus Eritematoso Sistémico/diagnóstico por imagen , Lupus Eritematoso Sistémico/psicología , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico por imagen , Vasculitis por Lupus del Sistema Nervioso Central/psicología , Adulto , Mapeo Encefálico , Cuerpo Calloso/patología , Imagen de Difusión Tensora/métodos , Femenino , Giro del Cíngulo/patología , Humanos , Lupus Eritematoso Sistémico/patología , Vasculitis por Lupus del Sistema Nervioso Central/patología , Imagen por Resonancia Magnética , Adulto JovenRESUMEN
OBJECTIVES: Belimumab has recently been approved for the treatment of systemic lupus erythematosus (SLE) refractory to standard therapy. Following one case of an SLE flare after cessation of belimumab, we hypothesized that this might lead to a rebound phenomenon and possible exacerbation of SLE. METHOD: Members of the Israeli Society of Rheumatology were contacted by e-mail and asked to report cases of an SLE flare following cessation of belimumab treatment. RESULTS: Three cases of SLE patients who experienced a severe SLE flare following cessation of belimumab therapy were reported. In all cases, belimumab was given as treatment for active mucocutaneous manifestations and/or polyarthritis with improvement in all three patients, one of whom achieved disease remission. In all three cases, patients experienced a severe flare in previously uninvolved major organ systems, including one case of class IV lupus nephritis accompanied by a new-onset severe headache with elevated cerebrospinal fluid (CSF) protein and white matter lesions on brain magnetic resonance imaging (MRI), one case of severe pneumonitis and haemolytic anaemia, and one case of a systemic flare, fatigue, arthritis, and severe abdominal pain. CONCLUSIONS: Belimumab therapy has been shown to be beneficial in the management of active SLE, mostly in patients with mucocutaneous and musculoskeletal manifestations. We suggest a possible rebound effect following cessation of belimumab that could be due to an increase in B-cell activating factor (BAFF) levels and lead to a disease flare. Future assessment of BAFF levels in patients stopping belimumab therapy and clinical correlation may support this hypothesis. Further studies are needed to confirm this observation.
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Anemia Hemolítica , Anticuerpos Monoclonales Humanizados/uso terapéutico , Progresión de la Enfermedad , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Nefritis Lúpica , Vasculitis por Lupus del Sistema Nervioso Central , Neumonía , Adulto , Encéfalo/patología , Femenino , Humanos , Persona de Mediana Edad , Inducción de Remisión , Índice de Severidad de la Enfermedad , Privación de Tratamiento , Adulto JovenRESUMEN
The fibromyalgia syndrome (FMS) is considered to result from the exposure of a genetically susceptible individual to various triggers, such as physical trauma, stress, viral infections etc. A possible role of vaccination in FMS etiology has been suspected. Our objective was to evaluate the efficacy and safety of influenza vaccination in FMS patients. Nineteen FMS patients underwent physical and dolorimetric examinations and answered the fibromyalgia impact questionnaire (FIQ), the widespread pain index (WPI) checklist and the symptoms severity scale (SSS), which are part of the 2010 diagnostic criteria. Thirty-eight healthy subjects were recruited as controls. All participants were vaccinated with the inactivated split virion influenza vaccine. Serum was collected for antibody titration. Six weeks after vaccination, sera were tested by hemagglutination (HI) against A/California (H1N1), A/Perth (H3N2) and B/Brisbane. Humoral response was defined as either a fourfold or greater increase in titer, or an increase from a non-protective baseline level of <1/40 to a level of 1/40. No severe vaccination reactions were observed. No significant change was observed between WPI, SSS and FIQ values before and after vaccination, indicating no worsening of FMS symptoms. Vaccine immunogenicity: Six weeks after vaccination, FMS patients showed a significant increase in geometric mean titers of HI antibody. The rates of sero-protection increased from 22.9% for H1N1 to 89.5% post-vaccination. A significant increase in HI antibody titers was also demonstrated among healthy controls. Influenza vaccination was both safe and effective in FMS patients. In view of these results, FMS patients should be encouraged to undergo influenza vaccination according to the standard WHO recommendations.
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Fibromialgia/fisiopatología , Vacunas contra la Influenza/efectos adversos , Vacunación/efectos adversos , Adulto , Anticuerpos Antivirales/biosíntesis , Anticuerpos Antivirales/sangre , Progresión de la Enfermedad , Femenino , Humanos , Inmunogenicidad Vacunal , Subtipo H3N2 del Virus de la Influenza A/inmunología , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Vacunas de Productos InactivadosRESUMEN
BACKGROUND: In a previous study performed 9 ± 3.6 years ago, 74 asymptomatic patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS) underwent lung function testing. A significantly low diffusion capacity (DLCO) ranging from 45% to 70% was recorded in 28 of the 74 (37.8%) patients who were all free of respiratory symptoms. AIM: The aim of this report is to assess the clinical importance and the predictive value of a low DLCO in asymptomatic patients with SLE or APS. METHODS: Asymptomatic patients with SLE and/or APS who were found to have a low DLCO in the previous study were contacted. Of the 28 patients, 15 were recruited and reevaluated in the current study (SLE with APS (n = 7), SLE without APS (n = 7); primary APS (n = 1)). A full history, physical examination, nail bed capillaroscopy, current laboratory tests and full lung function tests including DLCO were performed. RESULTS: During a surveillance period of 9 ± 3.6 years, none of the patients developed lung disease. Diffusion capacity corrected for alveolar volume (DLCO/VA) improved in the study group during this period from 60.4% ± 7.0 to 76.1% ± 11.2 (p < 0.0001). Lung function tests including total lung capacity (TLC) and forced expiratory volume in one second (FEV1) remained within normal limits. Capillaroscopy studies did not reveal changes compatible with scleroderma in any of the patients. CONCLUSION: Low DLCO findings on lung function testing does not have a positive predictive value for the development of future lung disease in patients with SLE, with or without APS, who are free of respiratory symptoms. Our results suggest that a finding of low DLCO in asymptomatic patients with SLE, with or without APS, does not necessarily require further evaluation and imaging and may improve spontaneously over time. Further studies in a larger group of patients are needed to validate these findings.
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Enfermedades Pulmonares/etiología , Lupus Eritematoso Sistémico/fisiopatología , Pruebas de Función Respiratoria/métodos , Adulto , Anciano , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/fisiopatología , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Enfermedades Pulmonares/fisiopatología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Angioscopía Microscópica , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Capacidad de Difusión Pulmonar/métodos , Capacidad Pulmonar Total/fisiologíaRESUMEN
OBJECTIVES: Yearly vaccination against influenza is currently recommended to patients with rheumatoid Arthritis (RA). Antibody and cell-mediated responses are both involved in the defense against influenza. Humoral responses to influenza vaccine are impaired in RA patients treated with rituximab (RTX). The objectives of this study were to comparatively assess cell mediated and humoral responses to influenza vaccination in RA patients with or without RTX-induced CD20 B-cell depletion. METHODS: Trivalent influenza subunit vaccine was administered to 46 RA patients and to 16 healthy controls. The RA group included 29 patients treated by RTX and 17 on conventional disease-modifying anti-rheumatic drugs (DMARDs), mostly methotrexate. Peripheral blood mononuclear cells and sera were obtained immediately before and 4-6 weeks after vaccination. Cell-mediated response to influenza antigens was evaluated by flow cytometry for activated CD4 T-cells. Humoral response was evaluated by haemagglutination inhibition assay. RESULTS: Cellular response: Cell-mediated responses were comparable in RTX-treated vs. DMARDs-treated patients. The recall postvaccination CD4+ cellular response was similar in RA patients and healthy controls. A positive correlation was found between CD19+ cell count on the day of vaccination and cellular response in RTX-treated RA patients. Humoral response: The antibody response rate was significantly impaired in the RTX group: being 26.4%, 68.4% and 47.1% in RTX-treated, DMARDs-treated and controls, respectively. CONCLUSION: Cellular immunity to influenza vaccination in RTX-treated patients was similar to DMARDs-treated patients and healthy controls, while humoral immunity was severely impaired. The preservation of cellular immunity may explain the relatively low rate of infection among B-cell depleted patients.
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Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/inmunología , Inmunidad Celular , Vacunas contra la Influenza/inmunología , Adulto , Anciano , Anticuerpos Antivirales/sangre , Formación de Anticuerpos/inmunología , Artritis Reumatoide/tratamiento farmacológico , Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Estudios de Casos y Controles , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Inmunidad Humoral , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/inmunología , Gripe Humana/prevención & control , Leucocitos Mononucleares/inmunología , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , RituximabRESUMEN
OBJECTIVE: To compare the performance of QuantiFERON-TB Gold (QFT-G) with that of the tuberculin skin test (TST) in detecting latent tuberculosis (LTBI) among patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: A total of 35 RA patients and 15 healthy controls underwent TST, QFT-G assays and chest X-ray and filled out a questionnaire on predisposing conditions for TB disease. Serum interferon gamma (IFN-gamma) levels were tested by an enzyme-linked immunosorbent assay. RESULTS: Forty-five per cent of RA patients had a TST > 5 mm vs. 26% in healthy controls. In the RA patients, QFT-G was positive in 11.4%, negative in 60% and indeterminate in 28.6%. The overall agreement between TST and QFT-G was significantly lower in the RA population than in controls (56% vs. 84%). No correlation was found between the use of prednisone, methotrexate and QFT-G results or agreement between TST and QFT-G. A low IFN-gamma level (<4 pg/ml) was found in 51.5% of the RA patients. No correlation was found between serum IFN-gamma levels and QFT-G results. CONCLUSION: The clinical significance of negative QFT-G in TST-positive patients with low TB risk remains to be assessed. The high rate of indeterminate results questions the clinical utility of QFT-G in the diagnosis of LTBI in RA patients.
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Artritis Reumatoide/complicaciones , Ensayo de Inmunoadsorción Enzimática , Interferón gamma/sangre , Tuberculosis Latente/diagnóstico , Mycobacterium/inmunología , Juego de Reactivos para Diagnóstico , Prueba de Tuberculina , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Tuberculosis Latente/diagnóstico por imagen , Tuberculosis Latente/microbiología , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Proyectos Piloto , Valor Predictivo de las Pruebas , Prednisona/uso terapéutico , Radiografía , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The purpose of this study was to assess and characterise verbal memory impairment in patients with systemic lupus erythematosus (SLE) by the Rey Auditory Verbal Learning Test (Rey AVLT). METHODS: 40 consecutive, unselected patients with SLE were evaluated with the Rey AVLT, a clinical and research tool for the study of multiple learning and memory measures. All patients were assessed for disease activity, damage, presence of antiphospholipid antibodies and depression. Findings were compared with those of 40 healthy controls matched for age, sex and education. RESULTS: The study group included 40 patients with SLE (37 females, 3 males), median age 33 years (range 20-59), median disease duration 8 years (range 0.3-32). The median disease activity measured by the SLE Disease Activity Index (SLEDAI) was 4 (range 0-16). Median damage measured by the SLICC/ACR (Systemic Lupus International Collaborating Clinics/American College of Rheumatology) damage index score was 0 (range 0-4). Depression was detected in 16/40 patients. Several aspects of the memory domain, as measured by the Rey AVLT, were impaired in the SLE group, using analysis of variance with repeated measures. The learning curve of patients with SLE was significantly less steep compared with that of controls, (p = 0.036), the rate of words omitted from trial to trial was higher in the SLE group (p = 0.034) and retrieval was less efficient in SLE compared with controls (p = 0.004). The significance of these findings was maintained after omitting patients with stroke or depression. CONCLUSION: Learning ability was impaired in patients with SLE with a poor and inefficient learning strategy, as reflected by an impaired learning curve, repeated omissions and impaired retrieval. This pattern of memory deficit resembles that seen in patients with frontal lobe damage and warrants further localising brain studies.
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Discapacidades para el Aprendizaje/etiología , Lupus Eritematoso Sistémico/psicología , Trastornos de la Memoria/etiología , Aprendizaje Verbal , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Discapacidades para el Aprendizaje/diagnóstico , Masculino , Trastornos de la Memoria/diagnóstico , Persona de Mediana Edad , Prevalencia , Psicofísica , Adulto JovenRESUMEN
OBJECTIVE: To present a case of severe interstitial nephritis with proteinuria in primary Sjögren's syndrome (pSS) and review the literature regarding renal disease and its management in pSS, aiming to suggest recommendations for treatment. METHODS: A search of MEDLINE (PubMed) was performed for review articles and case reports using the MESH terms: Sjögren syndrome; renal disease; interstitial nephritis (IN); glomerulonephritis (GN). RESULTS: We describe a rare case of pSS presenting with hypokalaemic tetraparesis and proteinuria due to severe IN, successfully treated with high-dose steroids and azathioprine. Reviewing the literature, we identified 180 reported cases of renal involvement in pSS (selected based on the European criteria for pSS), 89 of which underwent renal biopsies revealing IN in 49 cases, GN in 33 samples, and both IN and GN in seven. Eighteen studies reported treatment experience of renal disease in 32 pSS cases. Seventeen patients were treated with corticosteroids and cyclophosphamide, and 15 patients received only steroids with improvement in the majority of cases. CONCLUSION: The present case, as well as the limited number of reports in the literature, suggest that renal involvement, including IN, in pSS may improve with immunosuppressive therapy. Further studies are required to determine indications for and dosages of immunosuppressive treatment in patients with renal involvement of pSS.
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Inmunosupresores/uso terapéutico , Nefritis Intersticial/tratamiento farmacológico , Síndrome de Sjögren/tratamiento farmacológico , Femenino , Humanos , Persona de Mediana Edad , Nefritis Intersticial/etiología , Proteinuria/etiología , Síndrome de Sjögren/complicaciones , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess the effect of rituximab on the efficacy and safety of influenza virus vaccine in patients with rheumatoid arthritis (RA). METHODS: The study group comprised patients with RA treated with conventional disease-modifying drugs with or without rituximab. Split-virion inactivated vaccine containing 15 microg haemagglutinin/dose of B/Shanghai/361/02 (SHAN), A/New Caledonian/20/99 (NC) (H1N1) and A/California/7/04 (CAL) (H3N2) was used. Disease activity was assessed by the number of tender and swollen joints, duration of morning stiffness and evaluation of pain on the day of vaccination and 4 weeks later. CD19-positive cell levels were assessed in rituximab-treated patients. Haemagglutination inhibition (HI) antibodies were tested and response was defined as a greater than fourfold rise 4 weeks after vaccination or seroconversion in patients with a non-protective baseline level of antibodies (<1/40). Geometric mean titres (GMT) were calculated in all subjects. RESULTS: The participants were divided into three groups: RA (n = 29, aged 64 (12) years), rituximab-treated RA (n = 14, aged 53 (15) years) and healthy controls (n = 21, aged 58 (15) years). All baseline protective levels of HI antibodies and GMT were similar. Four weeks after vaccination, there was a significant increase in GMT for NC and CAL antigens in all subjects, but not for the SHAN antigen in the rituximab group. In rituximab-treated patients, the percentage of responders was low for all three antigens tested, achieving statistical significance for the CAL antigen. Measures of disease activity remained unchanged. CONCLUSION: Influenza virus vaccine generated a humoral response in all study patients with RA and controls. Although the response was significantly lower among rituximab-treated patients, treatment with rituximab does not preclude administration of vaccination against influenza.
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Anticuerpos Monoclonales/farmacología , Antirreumáticos/farmacología , Artritis Reumatoide/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Adulto , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Anticuerpos Antivirales/biosíntesis , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Femenino , Pruebas de Inhibición de Hemaglutinación/métodos , Humanos , Virus de la Influenza A/inmunología , Virus de la Influenza B/inmunología , Masculino , Persona de Mediana Edad , Rituximab , Índice de Severidad de la Enfermedad , VacunaciónRESUMEN
OBJECTIVE: To assess and compare parameters of pulmonary function in systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS) patients. METHODS: Consecutive patients (n = 74) who were free of respiratory symptoms were divided into four groups: 1) SLE (n = 23); 2) SLE with anti-phospholipid antibodies (aPL) (n = 18); 3) SLE with APS (n = 20); and 4) primary APS (PAPS) (n = 13). Pulmonary function testing, single breath diffusion capacity of carbon monoxide (DLCO/SB) and echocardiography studies were performed. Induced sputum cytology was analysed. RESULTS: Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and DLCO were significantly reduced in SLE compared to PAPS patients (p = 0.039; p = 0.017; p = 0.029, respectively). Elevated pulmonary arterial pressure was observed in two patients with SLE and aPL and in two with SLE and APS. Lymphocyte and eosinophil counts in induced sputum showed no significant differences; however, a trend towards lower CD4 counts in SLE vs. PAPS was noted (p = 0.086), while in patients with both SLE and APS, a low CD4/CD8 ratio was seen. Patients with APS were older than patients without APS (47.12+/-14.86 vs. 34.29+/-12.6, p = 0.0001), while SLE patients were younger than PAPS patients (38.19+/-14.68 vs. 48.53+/-13.97, p = 0.023). CONCLUSION: Abnormal pulmonary functions tests were detected frequently in asymptomatic patients with SLE or PAPS. Although SLE patients were younger, pulmonary function was significantly more impaired in SLE as compared to PAPS patients.
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Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/fisiopatología , Enfermedades Pulmonares/etiología , Lupus Eritematoso Sistémico/fisiopatología , Adulto , Edad de Inicio , Síndrome Antifosfolípido/patología , Volumen Espiratorio Forzado , Humanos , Enfermedades Pulmonares/patología , Persona de Mediana Edad , Pletismografía , Pruebas de Función Respiratoria , Esputo/química , Capacidad VitalRESUMEN
Somatostatin, a naturally occurring neuropeptide, is an immunomodulator which inhibits humoral and cell mediated immunity as well as secretion of proinflammatory cytokines. The objective of this study was to examine the effects of a somatostatin analogue on the severity of glomerulonephritis in the female NZB/W F1 murine model of systemic lupus erythematosus (SLE). Twenty female NZB/W F1 mice were treated at 23 weeks of age with 10 mg/kg of the somatostatin analogue Sandostatin- LAR, IM every four weeks. Ten control mice received IM injection of vehicle. Mice were assessed at four-week intervals for weight change, proteinuria, anti-DNA antibodies and splenocyte cytokine profile. The mice were sacrificed at age 34.5 weeks. Kidneys were collected and evaluated by light and immunofluorescence (IF) microscopy. Spleens were collected and splenocyte intracellular cytokines were measured by FACS analysis. In the treatment group significantly less proteinuria was observed four weeks after the second somatostatin analogue injection (dipstik scale: +2.07 +/- 0.95 versus. +3.5 +/- 1.08, P = 0.0002). The treated mice did not lose weight while the control group lost weight over time (P = 0.016). No differences were noted between the groups in anti-DNA antibody titres, cytokine profile or the severity of lupus nephritis as assessed by light and IF microscopy. Somatostatin analogue treatment attenuated proteinuria and prevented weight loss in NZB/W F1 mice, suggesting a possible beneficial effect on renal parameters and systemic manifestations of the disease. Further studies will be needed to assess the value of somatostatin analogue treatment in lupus nephritis, utilizing higher doses, at different stages of the disease, for longer periods.
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Lupus Eritematoso Sistémico/fisiopatología , Octreótido/uso terapéutico , Proteinuria/tratamiento farmacológico , Somatostatina/uso terapéutico , Pérdida de Peso/efectos de los fármacos , Animales , Anticuerpos Antinucleares/sangre , Antineoplásicos Hormonales/uso terapéutico , Peso Corporal/efectos de los fármacos , Citocinas/inmunología , Modelos Animales de Enfermedad , Femenino , Glomerulonefritis/tratamiento farmacológico , Glomerulonefritis/etiología , Glomerulonefritis/patología , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Ratones , Ratones Endogámicos , Proteinuria/complicaciones , Proteinuria/etiología , Somatostatina/análogos & derivados , Bazo/citología , Bazo/inmunologíaRESUMEN
B-Lymphocyte-activating factor (BAFF/BLyS) is a survival factor for B cells, belonging to the tumor necrosis ligand super family. Serum BAFF levels have been found to be elevated in patients with systemic lupus erythematosus (SLE). Neutralization of BAFF activity was suggested as an additional therapeutic approach in SLE. To determine the effect of add-on Quinacrine (Qn) treatment on serum BAFF levels and the effect of this treatment on SLE disease activity index (SLEDAI), antidsDNA and anticardiolipin (aCL) antibody levels, we treated 29 stable SLE patients, who were maintained on prednisolone and hydroxychloroquine and in some on azathioprine (AZT), with additional Qn (100 mg/d) with an aim to further reduce disease activity. SLEDAI, antidsDNA, aCL antibodies and serum BAFF levels were assessed before and 3 months after the addition of Qn. Three months following Qn initiation, a reduction in SLEDAI was noticed in 19/29 patients (mean 8.8 +/- 2.3 to 3.3 +/- 1.5, P = 0.009), followed by reduction or discontinuation of prednisolone in all patients and the discontinuation of AZT in five patients. Serum BAFF levels were significantly reduced in 8/12 patients (mean 6.3 +/- 0.5 to 3.0 +/- 0.56 ng/ml P = 0.0001). This reduction was found in correlation with a decrease in aCL titres. However, the decrease in SLEDAI scores and antidsDNA antibody titres was unrelated to the decrease in serum BAFF or aCL levels. We conclude that the addition of Qn to previous therapeutic regimens in active SLE is beneficial and seems to reduce SLEDAI scores, serum BAFF and aCL levels and therefore should be considered in many of our SLE patients before aggressive treatments are given.
Asunto(s)
Anticuerpos Anticardiolipina/análisis , Lupus Eritematoso Sistémico/tratamiento farmacológico , Proteínas de la Membrana/sangre , Quinacrina/uso terapéutico , Adulto , Antirreumáticos/uso terapéutico , Azatioprina/uso terapéutico , Factor Activador de Células B , Estudios de Casos y Controles , Quimioterapia Combinada , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Prednisolona/uso terapéutico , Quinacrina/administración & dosificación , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfaRESUMEN
OBJECTIVE: To assess the efficacy and safety of vaccination against influenza virus in patients with rheumatoid arthritis, with special emphasis on the effect of disease modifying antirheumatic drugs (DMARDs), including tumour necrosis factor alpha (TNFalpha) blockers. METHODS: 82 rheumatoid patients and 30 healthy controls were vaccinated with a split-virion inactivated vaccine containing 15 mug haemagglutinin (HA) per dose of each of B/Hong Kong/330/2001 (HK), A/Panama/2007/99 (PAN), and A/New Caledonian/20/99 (NC). Disease activity was assessed by tender and swollen joint count, morning stiffness, evaluation of pain, Health Assessment Questionnaire, ESR, and C reactive protein on the day of vaccination and six weeks later. Haemagglutination inhibiting (HI) antibodies were tested by a standard WHO procedure. Response was defined as a fourfold or more rise in HI antibodies six weeks after vaccination, or seroconversion in patients with a non-protective baseline level of antibodies (<1/40). Geometric mean titres (GMT) were calculated to assess the immunity of the whole group. RESULTS: Six weeks after vaccination, a significant increase in GMT for each antigen was observed in both groups, this being higher in the healthy group for HK (p=0.004). The percentage of responders was lower in rheumatoid patients than healthy controls (significant for HK). The percentage of responders was not affected by prednisone or any DMARD, including methotrexate, infliximab, and etanercept. Indices of disease activity remained unchanged. CONCLUSIONS: Influenza virus vaccine generated a good humoral response in rheumatoid patients, although lower than in healthy controls. The response was not affected by the use of prednisone or DMARDs.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/inmunología , Vacunas contra la Influenza/administración & dosificación , Anticuerpos Antivirales/inmunología , Antígenos Virales/sangre , Artritis Reumatoide/tratamiento farmacológico , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Virus de la Influenza A/inmunología , Virus de la Influenza B/inmunología , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
BACKGROUND: The CNS manifestations of the antiphospholipid syndrome (APS) can mimic multiple sclerosis both clinically and radiologically. OBJECTIVE: To compare evoked potential studies in APS patients and patients with multiple sclerosis with similar neurological disability. METHODS: 30 APS patients with CNS manifestations and 33 patients with definite multiple sclerosis and similar neurological disability underwent studies of visual evoked potentials (VEP), somatosensory evoked potentials (SSEP) in the upper and lower limbs (UL, LL), and sympathetic skin responses (SSR) in the upper and lower limbs. RESULTS: The neurological manifestations in the APS patients included stroke (n = 17), transient ischaemic attacks (n = 10), and severe headache with multiple white matter lesions on brain MRI (n = 3). Abnormal SSEP (LL), and SSR (UL; LL) were seen in APS patients (37%, 27%, and 30%, respectively) but VEP and UL SSEP were rarely abnormal (10% and 6%, respectively in APS v 58% and 33% in multiple sclerosis; p = 0.0005, p = 0.008). Mean VEP latencies were more prolonged in multiple sclerosis (116 ms v 101 ms, p<0.001). Only one APS patient had abnormal findings in all three evoked potential studies, compared with seven patients in the multiple sclerosis group (p = 0.04) CONCLUSIONS: Abnormal VEPs are uncommon in APS in contrast to multiple sclerosis. Coexisting abnormalities in all other evoked potentials were similarly rare in APS. In patients with brain MRI findings compatible either with multiple sclerosis or APS, normal evoked potential tests, and especially a normal VEP, may support the diagnosis of APS.
Asunto(s)
Síndrome Antifosfolípido/diagnóstico , Potenciales Evocados Somatosensoriales , Potenciales Evocados Visuales , Esclerosis Múltiple/diagnóstico , Adulto , Anciano , Síndrome Antifosfolípido/patología , Síndrome Antifosfolípido/fisiopatología , Encéfalo/patología , Diagnóstico Diferencial , Femenino , Respuesta Galvánica de la Piel , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/patología , Esclerosis Múltiple/fisiopatologíaRESUMEN
OBJECTIVE: The purpose of this cross-sectional survey was to obtain and analyze data on self-perceived efficacy of different types of complementary alternative medicine (CAM) by patients with various rheumatologic conditions. METHODS: Patients followed in rheumatology outpatient clinics were screened for the use of CAM. Patients reporting the use of CAM were asked to participate in face-to-face structured interviews, specifying the various CAM types they used, and grading their subjective impression of efficacy of each CAM type on a scale of 1-10. RESULTS: 350 consecutive patients were screened and 148 reported using CAM. In general, homeopathy and acupuncture were the most commonly used CAM types (44% and 41% of the CAM users, respectively). The mean number of different CAM methods used by a CAM user was 1.9 +/- 1.1. Patients with fibromyalgia used significantly more CAM methods (2.7 +/- 1.4, p = 0.005). On patients' self-perceived efficacy scale of 1-10, the mean score of the whole group was 5.3 +/- 3.2. Acupuncture and homeopathy achieved significantly higher self-perceived efficacy scores in CAM users with spondylo-arthropathies and osteoarthritis, respectively, when compared to some of the other disease groups. Satisfaction was lowest among CAM users with rheumatoid arthritis, vasculitis and connective tissue diseases. CONCLUSION: In general, CAM users were less than moderately satisfied with self-perceived-efficacy of CAM therapies. However efficacy of specific CAM methods differed significantly among patients in different disease groups.
Asunto(s)
Terapias Complementarias/métodos , Enfermedades Reumáticas/terapia , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
The benefit of combining quinacrine (Qn) with hydroxychloroquine (HCQ) in the treatment of systemic lupus erythematosus (SLE) was previously re-evaluated by us. In our current study we observed that, in 11 active SLE patients (SLEDAI score 5-12), the addition of Qn (100 mg/day) to their existing ongoing therapeutic regimens resulted in a significant attenuation of their previously persistent anticardiolipin antibody (aCL) response. This was in comparison with a matched non-Qn treated control group composed of 14 randomly chosen aCL-positive SLE patients with a similar SLEDAI score 6-10. Prior to Qn treatment the therapeutic regimens of 12 months' duration, included in all cases HCQ (400 mg/day), in many cases prednisone (P, 10-20 mg/day) and in some additional cases immunosuppressive drugs. SLEDAI scores and aCL levels were monitored during the entire follow-up period which totaled 24 months in the study group and 15-18 months in the controls. Along with the beneficial effect of the added Qn on SLEDAI scores, aCL disappearance was documented in eight of 11 patients and remained negative during 8-12 months of follow-up (P = 0.004), compared with such a change in only three of 14 non-Qn treated aCL-positive patients (P = 0.18). We conclude that the added Qn treatment to former established therapeutic protocols may eliminate aCL response in SLE patients. Whether this agent's effect is permanent needs further elucidation.