RESUMEN
PURPOSE: Assessing frailty, in head and neck cancer (HNC) patients is key when choosing appropriate treatment. Optimal screening is challenging, as it should be feasible and should avoid over-referral for comprehensive geriatric assessment (CGA) This study aims to evaluate the association between geriatric assessment using a new two-step care pathway, referral to geriatrician and adverse outcomes. METHODS: This institutional retrospective analysis on a prospective cohort analysed the multimodal geriatric assessment (GA) of newly diagnosed HNC patients. Uni- and multivariable logistic regression was performed to study the association between the screening tests, and referral to the geriatrician for complete geriatric screening, and adverse outcomes. RESULTS: This study included 539 patients, of whom 276 were screened. Patients who underwent the GA, were significantly older and more often had advanced tumour stages compared to non-screened patients. Referral to the geriatrician was done for 30.8% of patients. Of the 130 patients who underwent surgery, 26/130 (20%) experienced clinically relevant postoperative complications. Of the 184 patients who underwent (radio)chemotherapy, 50/184 (27.2%) had clinically relevant treatment-related toxicity. Age, treatment intensity, polypharmacy and cognitive deficits, were independently associated with referral to geriatrician. A medium to high risk of malnutrition was independently associated with acute radiation induced toxicity and adverse outcomes in general. CONCLUSION: The current study showed a 30.8% referral rate for CGA by a geriatrician. Age, treatment intensity, cognitive deficits and polypharmacy were associated with higher rates of referral. Furthermore, nutritional status was found to be an important negative factor for adverse treatment outcomes, that requires attention.
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Fragilidad , Evaluación Geriátrica , Neoplasias de Cabeza y Cuello , Humanos , Anciano , Masculino , Evaluación Geriátrica/métodos , Femenino , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/cirugía , Fragilidad/diagnóstico , Anciano de 80 o más Años , Estudios Prospectivos , Persona de Mediana Edad , Estudios Retrospectivos , Derivación y Consulta , Complicaciones Posoperatorias/epidemiologíaRESUMEN
Rituximab (RTX) treatment in rheumatoid arthritis (RA) patients severely hampers humoral response after influenza vaccination as determined by haemagglutination inhibition assay (HI). It is not known whether HI reflects both immunoglobulin (Ig)M and IgG (subclass) influenza response, and whether IgM antibodies contribute to the low rate of influenza infection seen in RA patients. Twenty RA patients on methotrexate (MTX), 23 on RTX and 28 healthy controls (HC) received trivalent influenza subunit vaccination. Before and 28 days after vaccination, H1N1- and H3N2-specific antibodies were measured by HI and by IgM and IgG (subclass) enzyme-linked immunosorbent assay (ELISA). B cell activating factor (BAFF) levels were determined in serum samples before vaccination. Vaccination induced a significant increase of IgM and IgG (IgG1 and IgG3) antibodies against both strains in the HC and MTX groups (all P < 0·01), but not in the RTX group. HI correlated significantly in all cases with IgG (IgG1) but not with IgM. In RTX late patients (RTX treatment 6-10 months before vaccination), IgG (IgG1 and IgG3) response to vaccination was restored, but not IgM response. BAFF levels were significantly increased in RA-RTX patients and correlated with total IgG levels. Haemagglutination inhibition assay, used as gold standard, detects primarily IgG (IgG1) responses. IgM- and IgG influenza-specific antibodies increase after vaccination in HC and RA patients except in patients on RTX treatment. BAFF levels are increased in both early and late RTX-treated patients, but do not correlate with an influenza-specific antibody response.
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Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/inmunología , Anticuerpos Antivirales/inmunología , Femenino , Pruebas de Inhibición de Hemaglutinación/métodos , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Rituximab , Vacunación/métodosRESUMEN
The objective of this study is to evaluate urinary high mobility group box 1 (HMGB1) levels as markers for active nephritis in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in comparison with urinary CD4(+) effector memory T cells and urinary monocyte chemoattractant protein-1 (MCP-1). Twenty-four AAV patients with active nephritis and 12 healthy controls (HC) were evaluated. In nine patients, samples were also obtained during remission. Urinary levels of HMGB1 were measured by Western blot. CD4(+) T cells and CD4(+) effector memory T cells (CD4(+) CD45RO(+) CCR7(-) ) were determined in urine and whole blood by flow cytometry. Measurement of urinary levels of MCP-1 and serum HMGB1 levels were performed by enzyme-linked immunosorbent assay (ELISA). AAV patients with active nephritis had higher median intensity of HMGB1 in urine than HC [10·3 (7·05-18·50) versus 5·8 (4·48-7·01); P = 0·004]. Both urinary HMGB1 and MCP-1 levels decreased significantly from active nephritis to remission. The urinary MCP-1/creatinine ratio correlated with Birmingham Vasculitis Activity Score (BVAS) (P = 0·042). No correlation was found between the HMGB1/creatinine ratio and 24-h proteinuria, estimated glomerular filtration rate (eGFR), MCP-1/creatinine ratio, BVAS and serum HMGB1. A positive correlation was found between urinary HMGB1/creatinine ratio and CD4(+) T cells/creatinine ratio (P = 0·028) and effector memory T cells/creatinine ratio (P = 0·039) in urine. Urinary HMGB1 levels are increased in AAV patients with active nephritis when compared with HC and patients in remission, and urinary HMGB1 levels are associated with CD4(+) T cells and CD4(+) effector memory T cells in urine. Measurement of urinary HMGB1 may be of additional value in identifying active glomerulonephritis in AAV patients.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Glomerulonefritis/etiología , Glomerulonefritis/orina , Proteína HMGB1/orina , Adulto , Anciano , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Biomarcadores , Quimiocina CCL2/orina , Femenino , Glomerulonefritis/sangre , Proteína HMGB1/sangre , Humanos , Memoria Inmunológica , Masculino , Persona de Mediana Edad , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismoRESUMEN
SUMMARY: Photosensitivity is characteristic of systemic lupus erythematosus (SLE). Upon ultraviolet B (UVB) exposure, patients develop inflammatory skin lesions in the vicinity of sunburn cells (SBCs). High mobility group box 1 (HMGB1) is released from apoptotic and activated cells and exerts inflammatory actions through ligation to its receptors. METHODS: Eleven SLE patients and 10 healthy controls (HCs) were exposed to UVB. Skin biopsies were taken before and at one, three and 10 days after irradiation. Sections were stained for SBC, HMGB1, CD3, CD68, interferon-induced protein MxA and cleaved caspase 3. In vitro experiments with UVB-irradiated keratinocytes were also performed. Higher numbers of cells that had released HMGB1 were seen in the skin of SLE patients compared to HCs before and after irradiation. HMGB1-negative nuclei correlated with the presence of SBCs, and with the number of cleaved caspase 3 positive cells in lupus skin. RESULTS: HMGB1 release is increased in the skin of SLE patients compared to HCs. Upon UVB exposure, HMGB1 release further increases in SLE patients and is related to the number of apoptotic cells. Our data suggest that HMGB1, probably released from apoptotic keratinocytes, contributes to the development of inflammatory lesions in the skin of SLE patients upon UVB exposure.
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Proteína HMGB1/metabolismo , Inflamación/etiología , Lupus Eritematoso Sistémico/complicaciones , Trastornos por Fotosensibilidad/etiología , Adulto , Apoptosis/efectos de la radiación , Biopsia , Estudios de Casos y Controles , Caspasa 3/metabolismo , Femenino , Humanos , Inflamación/diagnóstico , Queratinocitos/metabolismo , Queratinocitos/efectos de la radiación , Masculino , Persona de Mediana Edad , Trastornos por Fotosensibilidad/diagnóstico , Piel/metabolismo , Piel/patología , Piel/efectos de la radiación , Factores de Tiempo , Rayos Ultravioleta/efectos adversosRESUMEN
The European League Against Rheumatism (EULAR) recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) have been recently published. These evidence-based recommendations were based on existing literature in combination with expert opinion. Although patients with AIIRD are at increased risk of suffering from (complicated) infectious diseases--and vaccination seems a tool to reduce this risk--still many questions and controversies remain for the individual patient. In this overview, taking influenza as an example, the background of the recommendations, their clinical implications, and the direction of future research are discussed. The increase in knowledge on vaccine-preventable infections will allow us to further improve vaccination strategies.
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Enfermedades Autoinmunes/inmunología , Inmunización , Enfermedades Reumáticas/inmunología , Vacunas/inmunología , Contraindicaciones , Europa (Continente) , Guías como Asunto , Humanos , Gripe Humana/prevención & control , Vacunas/uso terapéuticoRESUMEN
Fatigue is a major problem in systemic lupus erythematosus (SLE), but the physiological substrate of this fatigue is largely unclear. To examine if low levels of dehydroepiandrosterone (DHEA) and its sulphate DHEAS play a role in SLE fatigue, we compared: 1) DHEAS levels and fatigue between 60 female patients with SLE with low disease activity (31 using, 29 not using prednisone) and 60 age-matched healthy women, and 2) fatigue between patients with SLE with low and normal DHEAS levels. Serum DHEAS levels were determined with an Advantage Chemiluminescense System. The Multidimensional Fatigue Inventory (MFI) was used to assess fatigue. Patients were more fatigued (p ≤ 0.001) than healthy women and more often had below-normal DHEAS levels (p < 0.001). Patients using prednisone with low and normal DHEAS levels reported a similar level of fatigue (p ≥ 0.39). Patients with low DHEAS levels not using prednisone reported less fatigue than those with normal DHEAS levels (p ≤ 0.03). Thus, our results indicate that low DHEAS levels in SLE are not - or even inversely - related to fatigue. After our previous finding that DHEA administration does not reduce fatigue, this result further indicates that low serum DHEA(S) levels alone do not offer an explanation for SLE fatigue.
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Sulfato de Deshidroepiandrosterona/sangre , Fatiga/etiología , Lupus Eritematoso Sistémico/fisiopatología , Prednisona/uso terapéutico , Adulto , Anciano , Estudios de Casos y Controles , Fatiga/epidemiología , Femenino , Glucocorticoides/uso terapéutico , Humanos , Mediciones Luminiscentes , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/tratamiento farmacológico , Persona de Mediana Edad , Psicometría , Adulto JovenRESUMEN
OBJECTIVE: Interaction of advanced glycation end products (AGEs) with their receptors (RAGE) plays an important role in inflammation in auto-immune diseases. Several functional polymorphisms of RAGE have been described. In this study we analysed the role of RAGE polymorphisms in disease susceptibility for systemic lupus erythematosus (SLE). In addition, we investigated whether these polymorphisms in SLE are associated with serum levels of soluble RAGE (sRAGE), renal involvement (lupus nephritis (LN)) and its outcome. METHODS: For this cross-sectional study DNA samples of 97 SLE patients, 114 LN patients and 429 healthy controls (HC) were genotyped for four RAGE polymorphisms: -429 T/C, -374 T/A, 2184 A/G and Gly82Ser. Differences in genotype frequencies and allele frequencies were tested between patients and HCs. In SLE patients, sRAGE was measured by enzyme-linked immunosorbent assay (ELISA). In addition, association of genotypes with sRAGE and disease severity in LN was analysed. RESULTS: The C allele of -429 T/C, the T allele of -374 T/A and the G allele of 2184 A/G were significantly more prevalent in SLE and LN compared with HC. In LN, the C allele of RAGE -429 T/C, the A allele of -374 T/A and the G allele of RAGE 2184 A/G polymorphism were significantly associated with more proteinuria and worse renal function during the first two years of treatment. No association of genotype with sRAGE was found. CONCLUSION: RAGE polymorphisms are associated with susceptibility to SLE and LN. In addition, some of these polymorphisms are likely to be associated with disease severity and initial response to treatment in LN.
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Lupus Eritematoso Sistémico/genética , Nefritis Lúpica/genética , Polimorfismo Genético , Receptores Inmunológicos/genética , Adulto , Anciano , Estudios Transversales , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Receptor para Productos Finales de Glicación AvanzadaRESUMEN
OBJECTIVES: Calcinosis cutis affects 20-40% of patients with systemic sclerosis (SSc). When calcinosis cutis becomes clinically apparent, it is irreversible in most cases. Detection of active calcification formation might allow early disease-modifying interventions. We assessed the feasibility of visualizing active calcifications using [18F]Sodium Fluoride ([18F]NaF) PET/low-dose CT (LDCT) in SSc patients with calcinosis cutis. METHODS: In this cross-sectional, observational pilot study patients underwent a whole body [18F]NaF PET/LDCT. All patients met the 2013 ACR/EULAR SSc criteria and had clinically detectable calcinosis cutis. (Sub)cutaneous calcifications were described by three investigators. RESULTS: Nine female patients were included (median age 59.0 years [IQR 51.5-70.5]). [18F]NaF uptake was mostly visible in the fingers (n=7) and knees (n=5). [18F]NaF PET showed calcifications in the fingers of 3 patients where calcifications were undetected on LDCT and in the clinic. Ninety-seven percent of [18F]NaF positive lesions was visible on LDCT. Of all lesions visible on LDCT, 70% was also visible on [18F]NaF PET. CONCLUSION: Imaging of active calcifications in SSc is feasible using [18F]NaF PET/LDCT. Seventy percent of calcifications on LDCT were [18F]NaF PET positive. Although these findings require replication, [18F]NaF PET/LDCT may detect active calcification formation, being potentially suitable for early disease-modifying interventions.
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Calcinosis , Esclerodermia Sistémica , Calcinosis/complicaciones , Calcinosis/diagnóstico por imagen , Estudios Transversales , Femenino , Radioisótopos de Flúor , Humanos , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones , Radiofármacos , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico por imagen , Fluoruro de SodioRESUMEN
Evidence-based recommendations for vaccination of paediatric patients with rheumatic diseases (PaedRD) were developed by following the EULAR standardised procedures for guideline development. The EULAR task force consisted of (paediatric) rheumatologists/immunologists, one expert in vaccine evaluation, one expert in public health and infectious disease control, and one epidemiologist. A systematic literature review was conducted in MEDLINE, EMBASE, and abstracts of the EULAR and American College of Rheumatology meetings of 2008/9. The level of evidence and strength of recommendation were based on customary scoring systems. Delphi voting was applied to assess the level of agreement between task force members. 107 papers and eight abstracts were used. The majority of papers considered seasonal influenza (41) or pneumococcal (23) vaccination. 26 studies were performed specifically in paediatric patients, and the majority in adult rheumatoid arthritis and systemic lupus erythematosus patients. Fifteen recommendations were developed with an overall agreement of 91.7%. More research is needed on the safety and immunogenicity of (live-attenuated) vaccination in PaedRD, particularly in those using biologicals, and the effect of vaccination on prevention of infections.
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Infecciones Oportunistas/prevención & control , Enfermedades Reumáticas/inmunología , Vacunación/normas , Antirreumáticos/efectos adversos , Niño , Contraindicaciones , Medicina Basada en la Evidencia/métodos , Humanos , Huésped Inmunocomprometido , Infecciones Oportunistas/complicaciones , Infecciones Oportunistas/inmunología , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/terapia , Vacunación/efectos adversos , Vacunación/métodos , Vacunas Atenuadas/efectos adversos , Vacunas Atenuadas/inmunología , Vacunas Conjugadas/efectos adversos , Vacunas Conjugadas/inmunologíaRESUMEN
OBJECTIVES: To develop evidence-based European League Against Rheumatism (EULAR) recommendations for vaccination in patients with autoimmune inflammatory rheumatic diseases (AIIRD). METHODS: A EULAR task force was composed of experts representing 11 European countries, consisting of eight rheumatologists, four clinical immunologists, one rheumatologist/clinical immunologist, one infectious disease physician, one nephrologist, one paediatrician/rheumatologist and one clinical epidemiologist. Key questions were formulated and the eligible spectrum of AIIRD, immunosuppressive drugs and vaccines were defined in order to perform a systematic literature review. A search was made of Medline from 1966 to October 2009 as well as abstracts from the EULAR meetings of 2008 and 2009 and the American College of Rheumatology (ACR) meetings of 2007 and 2008. Evidence was graded in categories I-IV, the strength of recommendations was graded in categories A-D and Delphi voting was applied to determine the level of agreement between the experts of the task force. RESULTS: Eight key questions and 13 recommendations addressing vaccination in patients with AIIRD were formulated. The strength of each recommendation was determined. Delphi voting revealed a very high level of agreement with the recommendations among the experts of the task force. Finally, a research agenda was proposed. CONCLUSION: Recommendations for vaccination in patients with AIIRD based on the currently available evidence and expert opinion were formulated. More research is needed, particularly regarding the incidence of vaccine-preventable infectious diseases and the safety of vaccination in patients with AIIRD.
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Enfermedades Autoinmunes/complicaciones , Infecciones Oportunistas/complicaciones , Infecciones Oportunistas/prevención & control , Enfermedades Reumáticas/complicaciones , Vacunación , Enfermedades Autoinmunes/tratamiento farmacológico , Técnica Delphi , Medicina Basada en la Evidencia/métodos , Humanos , Inmunosupresores/efectos adversos , Enfermedades Reumáticas/tratamiento farmacológicoRESUMEN
BACKGROUND: Cytochrome P450 2D6 (CYP2D6) has a crucial role in the metabolic conversion of tamoxifen into the active metabolite endoxifen. In this cohort study, the effect of CYP2D6-predicted phenotype, defined as the combined effect of CYP2D6 genetic variation and concomitant use of CYP2D6-inhibiting medication, on time to breast cancer progression (TTP) and overall survival (OS) in women who use tamoxifen for metastatic breast cancer (MBC) was examined. METHODS: We selected patients treated with tamoxifen (40 mg per day) for hormone receptor-positive MBC from whom a blood sample for pharmacogenetic analysis (CYP2D6*3, *4, *5, *6, *10 and *41) was available. Patient charts (n=102) were reviewed to assess TTP and OS, and to determine whether CYP2D6 inhibitors were prescribed during tamoxifen treatment. RESULTS: OS was significantly shorter in patients with a poor CYP2D6 metaboliser phenotype, compared with extensive metabolisers (HR=2.09; P=0.034; 95% CI: 1.06-4.12). Co-administration of CYP2D6 inhibitors alone was also associated with a worse OS (HR=3.55; P=0.002; 95% CI: 1.59-7.96) and TTP (HR=2.97; P=0.008; 95% CI: 1.33-6.67) compared with patients without CYP2D6 inhibitors. CONCLUSION: CYP2D6 phenotype is an important predictor of treatment outcome in women who are receiving tamoxifen for MBC. Co-administration of CYP2D6 inhibitors worsens treatment outcome of tamoxifen and should therefore be handled with care.
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Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Citocromo P-450 CYP2D6/metabolismo , Metástasis de la Neoplasia/tratamiento farmacológico , Tamoxifeno/uso terapéutico , Adulto , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/patología , Estudios de Cohortes , Citocromo P-450 CYP2D6/genética , Inhibidores del Citocromo P-450 CYP2D6 , Inhibidores Enzimáticos/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Farmacogenética , Fenotipo , Resultado del TratamientoRESUMEN
OBJECTIVE: Dehydroepiandrosterone (DHEA) has been reported to improve fatigue and reduced well-being. Both are major problems in patients with systemic lupus erythematosus (SLE), even with quiescent disease. Low serum DHEA levels are common in SLE. The present work investigates the effects of DHEA administration on fatigue, well-being and functioning in women with inactive SLE. METHODS: In a double-blind, randomised, placebo-controlled study, 60 female patients with inactive SLE received 200 mg oral DHEA or placebo. Primary outcome measures were general fatigue, depressive mood, mental well-being and physical functioning. Assessments were made before treatment, after 3, 6 and 12 months on medication, and 6 months after cessation of treatment. RESULTS: Patients from the DHEA and placebo group improved on general fatigue (p<0.001) and mental well-being (p=0.04). There was no differential effect of DHEA. The belief that DHEA had been used was a stronger predictor for improvement of general fatigue than the actual use of DHEA (p=0.04). CONCLUSIONS: The trial does not indicate an effect of daily 200 mg oral DHEA on fatigue and well-being, and therefore DHEA treatment is not recommended in unselected female patients with quiescent SLE. Clinical Trials Registration Number NCT00391924.
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Deshidroepiandrosterona/uso terapéutico , Fatiga/tratamiento farmacológico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Adulto , Anciano , Deshidroepiandrosterona/sangre , Depresión/tratamiento farmacológico , Depresión/etiología , Método Doble Ciego , Fatiga/sangre , Fatiga/etiología , Femenino , Estudios de Seguimiento , Humanos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/psicología , Persona de Mediana Edad , Testosterona/sangre , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Several findings link systemic lupus erythematosus (SLE) with C1q, the first molecule of the classical complement pathway. Polymorphisms of the C1qA gene are associated with low serum C1q levels in patients with cutaneous LE, but C1q polymorphisms have not been studied in patients with systemic lupus. OBJECTIVE: To determine whether polymorphisms of the C1q genes are associated with SLE, disease phenotypes, serum C1q and CH50 levels. METHODS: DNA for genetic analysis was obtained from 103 Caucasian patients with SLE and their family members. Five tag single nucleotide polymorphisms (tag SNPs) served as unique markers for underlying SNPs in the genes of the C1q protein. The pedigree disequilibrium test (PDT) was applied to trios to determine association of markers with SLE, SLE phenotypes, low serum C1q and low CH50. Single SNP association and haplotype analysis was also performed. RESULTS: The PDT revealed a significant association of the tag SNP rs631090 (covering the C1qB gene) with SLE (p = 0.02). Rs631090 was moderately associated with low serum C1q levels (p = 0.06). In addition, the tag SNPs rs292001 and rs294183 were associated with more severe SLE (Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) damage index score>0; p = 0.007 and p = 0.02, respectively). Haplotype analysis and single SNP association analysis showed no significant associations, but additional analyses revealed that marker rs587585 is associated with low serum C1q and CH50 levels. CONCLUSIONS: C1q polymorphisms are associated with SLE, serum C1q and CH50 levels in a stable founder population of patients with SLE. Although the studied population was small and allele frequencies were low, this is the first study to suggest an association of C1q polymorphisms with SLE.
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Complemento C1q/genética , Lupus Eritematoso Sistémico/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Cromosomas Humanos Par 1/genética , Complemento C1q/análisis , Ensayo de Actividad Hemolítica de Complemento , Vía Clásica del Complemento , Femenino , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Desequilibrio de Ligamiento , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
OBJECTIVES: Wegener's granulomatosis (WG) is a systemic vasculitis characterised by relapsing and remitting disease activity. Immunosuppressive drugs are used to control disease, but increase susceptibility to infection. Therefore, influenza vaccination should be considered in WG patients. This study was performed to assess the immunogenicity of influenza vaccination in WG patients. METHODS: A randomised, controlled trial was performed in WG patients with quiescent disease, defined as a Birmingham vasculitis activity score (BVAS) less than 2. Patients were randomly assigned to receive influenza vaccination (n = 49) or to participate as controls (n = 23). In addition, healthy controls (n = 49) were vaccinated. At entry and at 1 and 3-4 months after entry, antibody responses to vaccination were determined. Furthermore, disease activity was measured (BVAS), adverse effects were recorded and antineutrophil cytoplasmic autoantibody (ANCA) titres were determined. RESULTS: WG patients achieved high seroprotection rates to all three influenza strains, comparable with healthy controls. Only the A/H1N1 strain patients had a lower seroconversion rate (p = 0.002) and geometric mean titre (p = 0.037) than controls. After 1 month, one control and one vaccinated WG patient had developed active disease. At 3-4 months, two additional control patients had developed active disease compared with none of the vaccinated patients (p = 0.099). Vaccination did not influence ANCA titres. Adverse effects did not differ between patients and healthy controls. CONCLUSIONS: Influenza vaccination in WG patients with quiescent disease induced a sufficient antibody response. TRIAL REGISTRATION NUMBER: NTR1130.
Asunto(s)
Anticuerpos Antivirales/sangre , Granulomatosis con Poliangitis/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Orthomyxoviridae/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Femenino , Granulomatosis con Poliangitis/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/efectos adversos , Gripe Humana/prevención & control , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Vasculitis/inmunologíaRESUMEN
OBJECTIVES: The association of systemic lupus erythematosus (SLE) with the human leucocyte antigen (HLA) region is well known. In this study, we analysed the involvement of the HLA region in susceptibility for SLE in a stable founder, Caucasian population of SLE patients. METHODS: We performed an extensive screen of the entire HLA region on 103 SLE patients and family-based controls. Both single locus association analysis and haplotype sharing analysis were performed. The Additional Disease Locus Test (ADLT) was applied to examine the nature of the observed associations and to distinguish true causal associations from associations due to linkage disequilibrium (LD). RESULTS: Significant associations were observed at markers in the HLA class I, class II, and class III regions using both haplotype sharing and single locus methods. The haplotype sharing methods revealed the most significant difference at marker D6S1666 in the HLA class II region (p(HSS) = 0.00037, p(CROSS) = 1.7 x 10(-5)). The most significant result for single locus association was shown at marker D6S265 in the HLA class I region (p = 0.00019). The ADLT demonstrated that these markers represent independent associations. CONCLUSION: HLA class I, class II, and class III are associated with SLE, but only class I and class II contribute independently to increased risk of SLE.
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Predisposición Genética a la Enfermedad/epidemiología , Antígenos HLA-D/genética , Antígenos de Histocompatibilidad Clase I/genética , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/genética , Adulto , Edad de Inicio , Anciano , Alelos , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Regulación de la Expresión Génica , Pruebas Genéticas/métodos , Genotipo , Humanos , Incidencia , Desequilibrio de Ligamiento/genética , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Países Bajos , Linaje , Reacción en Cadena de la Polimerasa , Probabilidad , Medición de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
OBJECTIVE: Childhood-onset systemic lupus erythematosus (SLE) is a severe, lifelong, multisystem autoimmune disease. Long-term outcome data are limited. This study was undertaken to identify clinical characteristics and health-related quality of life (HRQoL) of adults with childhood-onset SLE. METHODS: Patients participated in a single study visit comprising a structured history and physical examination. Disease activity (scored using the SLE Disease Activity Index 2000 [SLEDAI-2K]), damage (scored using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), and HRQoL (scored using the Short Form 36 Health Survey) were assessed. Medical records were reviewed. RESULTS: In total, 111 childhood-onset SLE patients were included; the median disease duration was 20 years, 91% of patients were female, and 72% were white. Disease activity was low (median SLEDAI-2K score 4), and 71% of patients received prednisone, hydroxychloroquine (HCQ), and/or other disease-modifying antirheumatic drugs. The vast majority of new childhood-onset SLE-related manifestations developed within 2 years of diagnosis. Damage such as myocardial infarctions began occurring after 5 years. Most patients (62%) experienced damage, predominantly in the musculoskeletal, neuropsychiatric, and renal systems. Cerebrovascular accidents, renal transplants, replacement arthroplasties, and myocardial infarctions typically occurred at a young age (median age 20 years, 24 years, 34 years, and 39 years, respectively). Multivariate logistic regression analysis showed that damage accrual was associated with disease duration (odds ratio [OR] 1.15, P < 0.001), antiphospholipid antibody positivity (OR 3.56, P = 0.026), and hypertension (OR 3.21, P = 0.043). Current HCQ monotherapy was associated with an SDI score of 0 (OR 0.16, P = 0.009). In this cohort, HRQoL was impaired compared to the overall Dutch population. The presence of damage reduced HRQoL scores in 1 domain. High disease activity (SLEDAI-2K score ≥8) and changes in physical appearance strongly reduced HRQoL scores (in 4 of 8 domains and 7 of 8 domains, respectively). CONCLUSION: The majority of adults with childhood-onset SLE in this large cohort developed significant damage at a young age and had impaired HRQoL without achieving drug-free remission, illustrating the substantial impact of childhood-onset SLE on future life.
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Antirreumáticos/uso terapéutico , Glucocorticoides/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Calidad de Vida , Adolescente , Adulto , Edad de Inicio , Anciano , Anticuerpos Antifosfolípidos/inmunología , Niño , Preescolar , Femenino , Humanos , Hidroxicloroquina/uso terapéutico , Hipertensión/epidemiología , Trasplante de Riñón/estadística & datos numéricos , Modelos Logísticos , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/inmunología , Nefritis Lúpica/epidemiología , Nefritis Lúpica/cirugía , Vasculitis por Lupus del Sistema Nervioso Central/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Enfermedades Musculoesqueléticas/epidemiología , Infarto del Miocardio/epidemiología , Países Bajos/epidemiología , Oportunidad Relativa , Prednisona/uso terapéutico , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/epidemiología , Adulto JovenRESUMEN
INTRODUCTION: The antiphospholipid syndrome (APS) is defined by the occurrence of venous and/or arterial thrombosis and/or pregnancy-related morbidity, combined with the presence of antiphospholipid antibodies (aPL) and/or a lupus anticoagulant (LAC). Large, controlled, intervention trials in APS are limited. This paper aims to provide clinicians with an expert consensus on the management of APS. METHODS: Relevant papers were identified by literature search. Statements on diagnostics and treatment were extracted. During two consensus meetings, statements were discussed, followed by a Delphi procedure. Subsequently, a final paper was written. RESULTS: Diagnosis of APS includes the combination of thrombotic events and presence of aPL. Risk stratification on an individual base remains challenging. 'Triple positive' patients have highest risk of recurrent thrombosis. aPL titres > 99th percentile should be considered positive. No gold standard exists for aPL testing; guidance on assay characteristics as formulated by the International Society on Thrombosis and Haemostasis should be followed. Treatment with vitamin K-antagonists (VKA) with INR 2.0-3.0 is first-line treatment for a first or recurrent APS-related venous thrombotic event. Patients with first arterial thrombosis should be treated with clopidogrel or VKA with target INR 2.0-3.0. Treatment with direct oral anticoagulants is not recommended. Patients with catastrophic APS, recurrent thrombotic events or recurrent pregnancy morbidity should be referred to an expert centre. CONCLUSION: This consensus paper fills the gap between evidence-based medicine and daily clinical practice for the care of APS patients.
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Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/terapia , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/terapia , 4-Hidroxicumarinas/uso terapéutico , Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/complicaciones , Técnica Delphi , Femenino , Humanos , Indenos/uso terapéutico , Embarazo , Complicaciones del Embarazo/inmunología , Trombosis/inmunología , Trombosis/terapia , Vitamina K/antagonistas & inhibidores , Vitamina K/uso terapéuticoRESUMEN
OBJECTIVE: To investigate the involvement of type I interferons and endothelial cell adhesion molecules in the development of ultraviolet B (UVB)-induced systemic lupus erythaematosus (SLE) skin lesions. METHODS: A total of 19 SLE patients and 13 controls were irradiated with two minimal erythaemal doses(MED) of UVB. Subsequently, skin biopsies were analysed (immuno) histologically over 10 days, for expression of IFNalpha-induced MxA, numbers of plasmacytoid dendritic cells (pDC), and expression of endothelial cell adhesion molecules, namely E-selectin, ICAM-1, and L-selectin ligand. Additionally, MxA expression was compared to its expression in nine established cutaneous lupus erythaematosus(CLE) lesions of SLE patients. RESULTS: Before irradiation IFNalpha-induced MxA was expressed at significantly higher levels in non-lesional skin of SLE patients compared to healthy controls. In patients developing infiltrates upon UVB irradiation, MxA expression increased further, reaching expression levels similar to or exceeding levels in CLE-skin lesions. In these patients, MxA expression was sustained up to day 10, in contrast to patients not developing infiltrates in whom expression decreased. No noteworthy numbers of plasmacytoid dendritic cells (pDC) were detected in nonirradiated skin or at any time after UVB exposure in SLE patients or controls. MxA expression correlated with influx of T-cells and monocytes/macrophages, and with expression of E-selectin and ICAM-1. CONCLUSION: Development of UVB-induced SLE skin lesions involves a skewing towards production of Th1-associated cytokines, such as IFNalpha. In turn, this may lead to up-regulation of E-selectin and ICAM-1 resulting in recruitment of T-cells and macrophages.