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1.
Lupus ; 28(5): 651-657, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30982400

RESUMO

OBJECTIVES: Poor adherence to immunosuppressive treatment is common in patients with systemic lupus erythematosus and may identify those with lupus nephritis (LN) who have a poorer prognosis. Non-adherence has also been reported to be a potential adverse outcome predictor in renal transplantation (rTp). We investigated whether non-adherence is associated with increased rTp graft rejection and/or failure in patients with LN. METHODS: Patients with LN undergoing rTp in two major London hospitals were retrospectively included. Medical and electronic records were reviewed for documented concerns of non-adherence as well as laboratory biochemical drug levels. The role of non-adherence and other potential predictors of graft rejection/failure including demographics, comorbidities, age at systemic lupus erythematosus and LN diagnosis, type of LN, time on dialysis prior to rTp and medication use were investigated using logistic regression. RESULTS: Out of 361 patients with LN, 40 had rTp. During a median follow-up of 8.7 years, 17/40 (42.5%) of these patients had evidence of non-adherence. A total of 12 (30.0%) patients experienced graft rejection or failure or both. In the adherent group 2/23 (8.7%) had graft rejection, whilst in the non-adherent this rose to 5/17 (29.4%, p = 0.11). Graft failure was seen in 5/23 (21.7%) patients from the adherent group and 4/17 (23.5%) in the non-adherent group ( p = 0.89). Non-adherent patients had a trend towards increased graft rejection, hazard ratio 4.38, 95% confidence interval = 0.73-26.12, p = 0.11. Patients who spent more time on dialysis prior to rTp were more likely to be adherent to medication, p = 0.01. CONCLUSION: Poor adherence to immunosuppressive therapy is common and has been shown to associate with a trend towards increased graft failure in patients with LN requiring rTp. This is the first paper to report that shorter periods on dialysis prior to transplantation might lead to increased non-adherence in lupus patients.


Assuntos
Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim , Nefrite Lúpica/terapia , Adesão à Medicação/estatística & dados numéricos , Adulto , Progressão da Doença , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Modelos Logísticos , Londres , Lúpus Eritematoso Sistêmico , Masculino , Pessoa de Meia-Idade , Curva ROC , Diálise Renal , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
2.
Eur J Neurol ; 25(1): 13-23, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28816394

RESUMO

Inflammatory idiopathic myopathies are a group of autoimmune diseases affecting predominantly the proximal skeletal muscles, with raised muscle enzymes, with or without skin involvement and extramuscular organ involvement. Autoantibodies help to characterize patients into different clinical phenotypes. Successful treatment necessitates controlling inflammation early with corticosteroids and invariably requires additional immunosuppressive therapy. This review focuses on the aetiology, pathogenesis, clinical presentation, investigations and management of patients presenting with inflammatory idiopathic myopathies, predominantly focusing on polymyositis and antisynthetase syndrome.


Assuntos
Doenças Autoimunes/diagnóstico , Imunossupressores/uso terapêutico , Miosite/diagnóstico , Autoanticorpos/imunologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/patologia , Diagnóstico Diferencial , Humanos , Músculo Esquelético/patologia , Miosite/tratamento farmacológico , Miosite/patologia , Resultado do Tratamento
3.
Lupus ; 26(14): 1513-1516, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28534426

RESUMO

Immunological abnormalities seen in relatives of patients with autoimmune disorders can be useful in understanding the pathogenesis of the disease since, unlike in patients, they cannot result from the disease process or drug treatment. In this article we present a brief overview of our studies of the basic immunological status of close relatives of SLE patients. We looked at blood levels of IgG, IgM and antibodies to double-stranded DNA, as well as at NK cell numbers and cytotoxic activity and the levels of NKT, B and T cells. As many as 60% of relatives showed one or more abnormalities in these assays. Most notably there were increased levels of IgG in male and female relatives and a reduction of IgM in females. IgG correlated inversely with NKT cell numbers adding strength to the concept that the presence of IgG autoantibodies in patients is due to impaired regulation by NKT cells. IgM, on the other hand, correlated inversely with NK cells which may thus have a role in bringing about the reduced IgM seen in some patients. Immunological abnormalities were found to be more often associated with parents and offspring of patients than with their siblings, pointing to the involvement of environmental or epigenetic influences in lupus pathogenesis.


Assuntos
Saúde da Família , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Anticorpos Antinucleares/imunologia , Autoanticorpos/imunologia , Linfócitos B/imunologia , Feminino , Humanos , Células Matadoras Naturais/imunologia , Masculino , Linfócitos T/imunologia
4.
Lupus ; 26(1): 17-26, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27216418

RESUMO

OBJECTIVE: The objective of this study was to review the links between ethnicity, serology and clinical expression in systemic lupus erythematosus (SLE) in a single cohort that was followed over a 36-year period. PATIENTS AND METHODS: Patients with SLE treated at the University College London Hospitals (UCLHs) between January 1978 and December 2013 formed the cohort. We assessed the demographic, clinical and serological data. Standard methods were used for laboratory testing. The Student t test and Mann-Whitney U test were used for the continuous variables; the Fisher's exact test was used for the categorical variables. RESULTS: We studied 624 SLE patients: There were 571 women (91.5%), with a mean age at diagnosis of 29.0 ± 6.5 years; and 53 men (8.5%), with a mean age at diagnosis of 29.4 ± 15.3 years. Ethnically, 369 of the patients were European, 100 were Afro-Caribbean, 77 were East Asian, 56 were South Asian and 21 were of mixed ethnicity. The East Asian patients developed the disease at a younger age than the other ethnic groups (p < 0.0001). The Afro-Caribbean patients were less frequently associated with the presence of rash and photosensitivity, and the non-European patients were more likely to have alopecia and renal involvement. The South Asian patients were significantly associated with musculoskeletal and neurological involvement, serositis, Sicca syndrome and hematological features. The Afro-Caribbean patients had the highest prevalence of anti-Smith, anti-RNP, anti-Ro and anti-La antibodies. Anti-IgG anticardiolipin (aCL) antibodies were significantly associated with the non-East Asian groups; and hypocomplementemia was common in the East Asians. Rash, alopecia, mouth ulcers, serositis, neurological, joint and renal involvement were significantly associated with the presence of anti-Smith and anti-RNP antibodies in the Afro-Caribbean group. We also observed an association of joint involvement and the presence of anti-Ro and anti-La antibodies in this group. CONCLUSIONS: The East Asian patients developed their SLE disease at a younger age than the other ethnic groups. Cutaneous involvement was more frequent in those who were not Afro-Caribbean. Serositis, joint and neurological involvement were more frequently diagnosed in the South Asian patients. Anti-ENA antibodies were frequently associated with the Afro-Caribbean patients.


Assuntos
Povo Asiático/estatística & dados numéricos , População Negra/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/epidemiologia , Adolescente , Adulto , Idade de Início , Idoso , Anticorpos Antinucleares/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Pessoa de Meia-Idade , Testes Sorológicos , Estatísticas não Paramétricas , População Branca/estatística & dados numéricos , Adulto Jovem
5.
Lupus ; 26(10): 1051-1059, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28420054

RESUMO

Autoantibodies to dense fine speckles 70 (DFS70) are purported to rule out the diagnosis of SLE when they occur in the absence of other SLE-related autoantibodies. This study is the first to report the prevalence of anti-DFS70 in an early, multinational inception SLE cohort and examine demographic, clinical, and autoantibody associations. Patients were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. The association between anti-DFS70 and multiple parameters in 1137 patients was assessed using univariate and multivariate logistic regression. The frequency of anti-DFS70 was 7.1% (95% CI: 5.7-8.8%), while only 1.1% (95% CI: 0.6-1.9%) were monospecific for anti-DFS70. In multivariate analysis, patients with musculoskeletal activity (Odds Ratio (OR) 1.24 [95% CI: 1.10, 1.41]) or with anti-ß2 glycoprotein 1 (OR 2.17 [95% CI: 1.22, 3.87]) were more likely and patients with anti-dsDNA (OR 0.53 [95% CI: 0.31, 0.92]) or anti-SSB/La (OR 0.25 [95% CI: 0.08, 0.81]) were less likely to have anti-DFS70. In this study, the prevalence of anti-DFS70 was higher than the range previously published for adult SLE (7.1 versus 0-2.8%) and was associated with musculoskeletal activity and anti-ß2 glycoprotein 1 autoantibodies. However, 'monospecific' anti-DFS70 autoantibodies were rare (1.1%) and therefore may be helpful to discriminate between ANA-positive healthy individuals and SLE.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/imunologia , Autoanticorpos/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Fatores de Transcrição/imunologia , beta 2-Glicoproteína I/imunologia , Adulto , Estudos de Coortes , Feminino , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Prevalência
6.
Ann Rheum Dis ; 75(2): 323-31, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26338095

RESUMO

OBJECTIVES: Evaluate efficacy and safety of tabalumab, a human IgG4 monoclonal antibody that binds and neutralises membrane and soluble B-cell activating factor (BAFF) versus placebo plus standard of care (SoC) in patients with systemic lupus erythematosus (SLE). METHODS: This phase III, 52-week study randomised 1164 patients with moderate-to-severe SLE (Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index ≥6 at baseline). Patients received SoC plus subcutaneous injections of tabalumab or placebo, starting with a loading dose (240 mg) at week 0 and followed by 120 mg every two weeks (120 Q2W, n=387), 120 mg every four weeks (120 Q4W, n=389) or placebo Q2W (n=388). PRIMARY ENDPOINT: proportion of patients achieving SLE Responder Index 5 (SRI-5) response at week 52. RESULTS: Similar proportions of patients in each group achieved SRI-5 response at week 52 (120 Q2W: 31.8%; 120 Q4W: 35.2% and placebo: 29.3%). Key secondary endpoints were not met. In a sensitivity analysis not excluding patients who decreased antimalarials or immunosuppressants, SRI-5 response was achieved with 120 Q4W (37.0% vs 29.8% placebo; p=0.021), but not 120 Q2W (34.1%; p=0.171). Significant reductions in anti-dsDNA antibodies, increases in C3 and C4, and reductions in total B cells and immunoglobulins were observed with tabalumab. No differences were observed between treatment groups in percentage of deaths (120 Q2W: 0.8%; 120 Q4W: 0.5%; placebo: 0.5%), serious adverse events (AEs) (range 11.1-14.4%) or treatment-emergent AEs (range 81.1-82.3%). CONCLUSIONS: Tabalumab had biological activity-changes in anti-dsDNA, complement, B cells and immunoglobulins-consistent with BAFF pathway inhibition. Key clinical efficacy endpoints did not achieve statistical significance. Safety profiles were similar with tabalumab and placebo. TRIAL REGISTRATION NUMBER: NCT01196091.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Fator Ativador de Células B/antagonistas & inibidores , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antinucleares/sangue , Anticorpos Monoclonais Humanizados , Autoanticorpos/sangue , Fator Ativador de Células B/administração & dosagem , Linfócitos B/metabolismo , Biomarcadores/sangue , População Negra , Complemento C3/metabolismo , Complemento C4/metabolismo , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
7.
Lupus ; 25(14): 1509-1519, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27329649

RESUMO

The association of systemic lupus erythematosus (SLE) with gastrointestinal autoimmune diseases is rare, but has been described in the literature, mostly as case reports. However, some of these diseases may be very severe, thus a correct and early diagnosis with appropriate management are fundamental. We have analysed our data from the SLE patient cohort at University College Hospital London, established in 1978, identifying those patients with an associated autoimmune gastrointestinal disease. We have also undertaken a review of the literature describing the major autoimmune gastrointestinal pathologies which may be coincident with SLE, focusing on the incidence, clinical and laboratory (particularly antibody) findings, common aetiopathogenesis and complications.


Assuntos
Doenças do Sistema Digestório/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Doença Celíaca/epidemiologia , Enterite/epidemiologia , Hepatite Autoimune/epidemiologia , Hospitais Universitários , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Cirrose Hepática Biliar/epidemiologia , Londres , Pancreatite/epidemiologia
8.
Lupus ; 25(14): 1542-1550, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27147622

RESUMO

OBJECTIVES: Significant differences have been reported in disease phenotype and severity of systemic lupus erythematosus (SLE) presenting in different age groups. Most indicate a more severe phenotype in juvenile-onset SLE (JSLE). There have been limited studies in older patients and no large studies looking at SLE across all age groups. METHODS: We assessed the effect of age of onset of SLE on the clinical phenotype by analysing data from two large UK cohorts (the UK JSLE Cohort and the UCLH SLE cohort). RESULTS: A total of 924 individuals were compared (413 JSLE, 511 adult-onset SLE). A female preponderance was present, but less pronounced at either end of the age spectrum. Arthritis was more common with advancing age (93% vs 72%, p < 0.001), whereas renal disease (44% vs 33%, p = 0.001), alopecia (47% vs 23%, p < 0.001) and aphthous ulcerations (39% vs 26%, p = 0.001) were more common in the young. Neuropsychiatric lupus was less common in mature-onset SLE (p < 0.01). JSLE was associated more commonly with thrombocytopenia (21% vs 15%, p = 0.01), haemolytic anaemia (20% vs 3%, p < 0.001), high anti-dsDNA (71% vs 63%, p = 0.009), Sm (22% vs 16%, p = 0.02) and RNP (36% vs 29%, p < 0.04) auto-antibodies. Leucopenia increased with advancing age (p < 0.001). Mortality has been declining over recent decades. However, death rates were substantially higher than the general population. The standardized mortality ratio was 18.3 in JSLE and 3.1 in adult-onset SLE. CONCLUSION: These data from the largest-ever direct comparison of JSLE with adult-onset SLE suggest an aggressive phenotype of disease with a worse outcome in patients with JSLE and emphasizes the importance of careful follow-up in this population.


Assuntos
Doenças Cardiovasculares/epidemiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Fenótipo , Adolescente , Adulto , Distribuição por Idade , Idade de Início , Criança , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Londres , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/mortalidade , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Centros de Atenção Terciária , Adulto Jovem
9.
Genes Immun ; 16(7): 470-80, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26291516

RESUMO

Autoimmune muscle diseases (myositis) comprise a group of complex phenotypes influenced by genetic and environmental factors. To identify genetic risk factors in patients of European ancestry, we conducted a genome-wide association study (GWAS) of the major myositis phenotypes in a total of 1710 cases, which included 705 adult dermatomyositis, 473 juvenile dermatomyositis, 532 polymyositis and 202 adult dermatomyositis, juvenile dermatomyositis or polymyositis patients with anti-histidyl-tRNA synthetase (anti-Jo-1) autoantibodies, and compared them with 4724 controls. Single-nucleotide polymorphisms showing strong associations (P<5×10(-8)) in GWAS were identified in the major histocompatibility complex (MHC) region for all myositis phenotypes together, as well as for the four clinical and autoantibody phenotypes studied separately. Imputation and regression analyses found that alleles comprising the human leukocyte antigen (HLA) 8.1 ancestral haplotype (AH8.1) defined essentially all the genetic risk in the phenotypes studied. Although the HLA DRB1*03:01 allele showed slightly stronger associations with adult and juvenile dermatomyositis, and HLA B*08:01 with polymyositis and anti-Jo-1 autoantibody-positive myositis, multiple alleles of AH8.1 were required for the full risk effects. Our findings establish that alleles of the AH8.1 comprise the primary genetic risk factors associated with the major myositis phenotypes in geographically diverse Caucasian populations.


Assuntos
Alelos , Antígenos HLA/genética , Miosite/genética , Adolescente , Adulto , Autoanticorpos/imunologia , Estudos de Casos e Controles , Dermatomiosite/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Polimiosite/genética , Fatores de Risco , População Branca
10.
Lupus ; 24(1): 42-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25124676

RESUMO

OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information and blood samples were obtained in a cross-sectional study from patients with SLE (n = 308) and other rheumatologic diseases (n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. RESULTS: Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8-4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI: 1.7-5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2-5.4, p = 0.015), anti-dsDNA (OR = 3.4, 95% CI: 1.9-6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI: 1.5-5.0, p = 0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3, 95% CI: 1.3-4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8-38.4, p < 0.01). CONCLUSIONS: Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis.


Assuntos
Anticorpos Antinucleares/sangue , Complemento C1q/imunologia , DNA/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Estudos de Casos e Controles , Proteínas do Sistema Complemento/deficiência , Estudos Transversais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/etnologia , Nefrite Lúpica/etnologia , Nefrite Lúpica/imunologia , Masculino , Pessoa de Meia-Idade , Proteinúria/sangue , Doenças Reumáticas/imunologia , Sensibilidade e Especificidade , Adulto Jovem
11.
Lupus ; 23(6): 545-53, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24557776

RESUMO

Drug-induced lupus erythematosus is defined as a syndrome with clinical and serological features similar to systemic lupus erythematosus that is temporally related to continuous drug exposure and which resolves after discontinuation of this drug. More than 90 drugs, including biological modulators such as tumour necrosis factor-α inhibitors and interferons, have been identified as likely 'culprits'. While there are no standard diagnostic criteria for drug-induced lupus erythematosus, guidelines that can help to distinguish drug-induced lupus erythematosus from systemic lupus erythematosus have been proposed and several different patterns of drug-induced lupus erythematosus are emerging. Distinguishing drug-induced lupus erythematosus from systemic lupus erythematosus is important because the prognosis of drug-induced lupus erythematosus is usually good when the drug is withdrawn. This review discusses the differences between drug-induced lupus erythematosus and systemic lupus erythematosus, the mechanisms of action of drug-induced lupus erythematosus and drugs that are usually associated with drug-induced lupus erythematosus, with particular focus on the biological treatments.


Assuntos
Autoimunidade/efeitos dos fármacos , Produtos Biológicos/efeitos adversos , Interferons/efeitos adversos , Lúpus Eritematoso Sistêmico/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/terapia , Prognóstico , Medição de Risco , Fatores de Risco
12.
Lupus ; 23(3): 273-83, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24356612

RESUMO

OBJECTIVES: The aim of the Systemic LUpus Erythematosus Cost of Care In Europe (LUCIE) study was to evaluate the annual direct medical costs of managing adults with active autoantibody-positive disease on medication for SLE in secondary care. This paper presents the UK analyses only. METHODS: A cost-of-illness study was conducted from the perspective of the National Health Service. Health resource utilization data were retrieved over a two-year period from four centres in England and unit cost data were taken from published sources. RESULTS: At baseline, 86 patients were included, 38 (44.2%) had severe SLE and 48 (55.8%) had non-severe SLE. The mean (SD) SELENA-SLEDAI score was 7.7 (5.7). The mean (SD) annual direct medical cost of was estimated at £3231 (£2333) per patient and was 2.2 times higher in patients with severe SLE compared with patients with non-severe SLE (p < 0.001). Multivariate model analyses showed that renal disease involvement (p = 0.0016) and severe flares (p = 0.0001) were associated with higher annual direct costs. CONCLUSIONS: Improvement of the overall stability of SLE and early intervention to minimize the impact of renal disease may be two approaches to mitigate the long-term direct cost of managing SLE patients in the UK.


Assuntos
Autoanticorpos/sangue , Custos de Cuidados de Saúde , Lúpus Eritematoso Sistêmico/economia , Lúpus Eritematoso Sistêmico/terapia , Avaliação de Processos e Resultados em Cuidados de Saúde/economia , Medicina Estatal/economia , Adulto , Biomarcadores/sangue , Controle de Custos , Análise Custo-Benefício , Progressão da Doença , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/sangue , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/economia , Nefrite Lúpica/terapia , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Análise Multivariada , Prevalência , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Reino Unido/epidemiologia
13.
Clin Exp Rheumatol ; 32(2): 188-93, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24447373

RESUMO

OBJECTIVES: Several factors have been implicated in the prognosis of idiopathic inflammatory myopathies, including age, gender, delay in diagnosis, neoplasia, creatine kinase levels and some autoantibodies. We have reviewed the main factors contributing to mortality in patients with idiopathic inflammatory myopathy (IIM) diagnosed between 1976 and 2007 who were followed for at least 5 years in the Rheumatology Unit at University College Hospital in London. METHODS: An observational retrospective study was carried out on patients with IIM diagnosed between 1976 and 2007. All the patients fullfilled at least three out of four of the Bohan and Peter criteria. The subjects were divided into the following groups: adult-onset polymyositis (APM); adult-onset dermatomyositis (ADM); juvenile dermatomyositis (JDM); Overlap syndromes with another autoimmune rheumatic disease. RESULTS: 90 patients were identified. The female to male ratio was 2.5:1 and the mean age at diagnosis was 38.5 years (SD 15.03). 47.8% of the patients had APM, 30% adult-onset ADM, 15.6% Overlap and 6.7% JDM. Among the extramuscular features, 18.9% had pulmonary involvement. In 70% the highest CK was >5 times the upper normal. Prednisolone was prescribed in 98.9%. 11.1% received rituximab. 34.4% had monophasic, 31.1% relapsing and remitting and 34.4% continuous progressive course of the disease. The median follow-up was 11.5 years (IQR 12.00). 14.4% of the patients died, 30.8% due to infection, 30.8% from a cardiovascular event and 23.1% due to neoplasia. The 1, 5 and 10-year survival was 100%, 97.8% and 91%, respectively. Male gender (Hazards Ratio (HR) 3.222; p=0.037), pulmonary involvement (HR 5.247; p=0.009), chronic progressive course (HR 3.711; p=0.030) and use of rituximab (HR 3.562; p=0.036) were the only risk factors to be statistically significantly associated (p<0.05) with death. CONCLUSIONS: We conclude that long-term survival in these patients is generally quite good with an estimated 10-year survival >90% in our cohort, which is even higher than previously reported.


Assuntos
Antirreumáticos/uso terapêutico , Miosite , Adulto , Idade de Início , Autoanticorpos/análise , Autoanticorpos/classificação , Creatina Quinase/análise , Diagnóstico Tardio/efeitos adversos , Diagnóstico Tardio/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Miosite/diagnóstico , Miosite/tratamento farmacológico , Miosite/epidemiologia , Miosite/etiologia , Miosite/fisiopatologia , Neoplasias/complicações , Neoplasias/epidemiologia , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Análise de Sobrevida
14.
Clin Exp Rheumatol ; 32(3): 301-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24708901

RESUMO

OBJECTIVES: To characterise long-term activity levels after renal failure (RF) in lupus patients. METHODS: A retrospective activity analysis was performed of 32 lupus nephritis (LN) patients in RF over a maximum of 34 years. Activity was recorded every 6 months using the BILAG index and serological involvement (SI) (C3 and anti-dsDNA antibodies). 'Inactive' disease was defined as no BILAG A/B and no SI, 'moderate disease' as at least BILAG 1A/ 2B or 'major' SI (C3<0.73g/L and/or anti-dsDNA>149IU/ml, and 'severe' as both BILAG 1 A/2B and major SI. Patients on dialysis (n=32) were compared to patients who had a renal transplantation (n=14). RESULTS: In the dialysis group, 12.5% were inactive and 87.5% had at least mild-moderate activity (92.8% due to SI; 85.7% due to clinical activity) of which 37.5% demonstrated severe activity. BILAG involvement was mainly haematological (59.4%) and mucocutaneous (25%). In the renal transplantation group, 92.8% were active (100% due to SI, 84.6% due to clinical activity) of which 28.6% displayed severe activity. BILAG involvement was mainly haematological (57.1%) and renal (50%). CONCLUSIONS: Although lupus activity is highly prevalent after RF, when a more restrictive cut off is established, activity decreases from 87.5% to 37.5% in the dialysis group and 92.8% to 28.6% in the renal transplantation group. Serological markers and haematological BILAG activity were the predominant indicators for post-RF lupus activity. We were unable to rule out whether activity derived from an intercurrent process or was intrinsic to the renal failure itself.


Assuntos
Falência Renal Crônica/epidemiologia , Falência Renal Crônica/fisiopatologia , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/fisiopatologia , Adulto , Biomarcadores , Feminino , Seguimentos , Humanos , Falência Renal Crônica/terapia , Transplante de Rim , Nefrite Lúpica/terapia , Masculino , Pessoa de Meia-Idade , Prevalência , Diálise Renal , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
15.
Lupus ; 22(9): 919-27, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23857987

RESUMO

OBJECTIVES: We determined whether any individual cancers are increased or decreased in a cohort of 595 patients with systemic lupus erythematosus (SLE) followed for up to 32 years at the University College London Hospitals Lupus Clinic, looking for any associated clinical or serological factors and the prognosis after cancer diagnosis. METHODS: We undertook a careful retrospective review of the medical records and identified all individuals diagnosed with cancer. For controls, we selected three other patients in the cohort who had not developed cancer, carefully matched for age, sex, ethnicity and disease duration, to determine if any obvious differences emerged in a nested case-control design. RESULTS: Thirty-three patients developed cancer after being diagnosed with SLE. There was a statistically insignificant small increase in overall cancer risk, standardized incidence ratios (SIRs) 1.05 (95% CI 0.52-1.58) and increased SIRs for cervical, prostate, anal and pancreatic cancers and reduction in breast cancer SIRs. Haematological and musculoskeletal manifestations, anticardiolipin and antithyroid globulin antibodies were found to be positively associated with cancer risk in multivariate analysis. There was no drug, dose or duration was associated with cancer risk. There was a reduction in survival with a cancer fatality rate of 84.2% (p < 0.0001). CONCLUSION: We found a very small but statistically insignificant increased cancer risk with reduction in survival. Whereas some cancers appear to be more common in SLE, notably prostate and cervical cancer, others, particularly breast cancer, are less frequent. Multiple clinical and serological factors are involved in the increased risk of malignancy in SLE. No drug dose or duration effect was identified.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Neoplasias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/patologia , Prognóstico , Estudos Retrospectivos , Risco , Taxa de Sobrevida , Adulto Jovem
16.
Lupus ; 22(9): 932-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23894047

RESUMO

Cutaneous manifestations occur frequently in systemic lupus erythematosus (SLE) and are pathognomonic in subacute-cutaneous lupus erythematosus (SCLE) and chronic cutaneous lupus erythematosus (CCLE). Although B-cell depletion therapy (BCDT) has demonstrated efficacy in SLE with visceral involvement, its usefulness for patients with predominant skin manifestations has not been fully established. In this single-centre, retrospective study 14 consecutive SLE, one CCLE and two SCLE patients with recalcitrant skin involvement were treated with 2 × rituximab 1 g, and 1 × cyclophosphamide 750 mg. Six months after BCDT, nine of 17 (53%) patients were in complete (CR) or partial remission (PR). Relapses occurred in 12 patients (71%) at a mean time of 10 ± 1.8 months after BCDT. A second cycle of BCDT achieved a more sustained remission in seven of nine patients (78%) lasting for a mean time of 18.4 ± 2.7 months. Minor adverse events were experienced by three patients. Mean follow-up was 30 months. Our own results and the literature review demonstrate that BCDT based on rituximab is well tolerated and may be effective for cutaneous lesions of lupus erythematosus. Randomized controlled trials are necessary to further evaluate the value of BCDT for this group of patients.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Linfócitos B/imunologia , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Anticorpos Monoclonais Murinos/efeitos adversos , Estudos de Coortes , Feminino , Seguimentos , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Lúpus Eritematoso Cutâneo/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Rituximab
17.
Lupus ; 22(10): 1070-6, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23864039

RESUMO

We describe a female patient with systemic lupus erythematosus (SLE) also diagnosed with Fabry's disease and anti-phospholipid antibody syndrome (APS). SLE and Fabry's disease are both systemic diseases with variable clinical presentations. Recent studies have shown a relatively high incidence of late onset Fabry's disease in female heterozygous individuals, suggesting that this condition could be under-diagnosed. We discuss a possible association between SLE and Fabry's disease and consider the role of lipid abnormalities in the pathogenesis of SLE.


Assuntos
Síndrome Antifosfolipídica/complicações , Doença de Fabry/complicações , Insuficiência Cardíaca/etiologia , Lúpus Eritematoso Sistêmico/complicações , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Lúpus Eritematoso Sistêmico/etiologia
18.
Scand J Rheumatol ; 42(1): 1-10, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23130978

RESUMO

OBJECTIVES: In this review we focus on the evidence for an association between musculoskeletal (MSK) manifestations and diabetes mellitus (DM). METHOD: A systematic literature review was performed using the PubMed database for articles that have been published in the past 8 years (from January 2003 to August 2011) for keywords referring to MSK manifestations and DM. Where possible we have distinguished between manifestations that occur in type 1 as opposed to type 2 DM. However, this was not easy because many reports do not make the distinction. RESULTS: MSK manifestations of DM are relatively common. The duration of DM is often linked to the onset of some MSK features. CONCLUSIONS: Patients with DM have been reported to have an increased prevalence of several MSK manifestations. It is important to be aware of MSK complications of DM. A better control of the glucose level may be useful.


Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Doenças Musculoesqueléticas/epidemiologia , Doenças Reumáticas/epidemiologia , Humanos , Prevalência
20.
Lupus ; 21(10): 1041-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22505605

RESUMO

OBJECTIVE: To review the differences between male and female lupus patients with respect to clinical features, serology and outcome over a thirty year period. MATERIAL AND METHODS: An observational study of all SLE patients seen at University College of London Hospital between 1976 and 2005 was performed. Demographic, clinical and serological data and outcome were retrospectively collected from hospital records or questionnaires and reviewed. Comparisons between continuous variables were made using the Kruskal-Wallis test and Student's t-test. Chi-square test or Fisher´s exact test were used for categorical variables when it was appropriate. RESULTS: A total of 484 patients (439 females and 45 males) were identified between 1976 and 2005. Their mean age at diagnosis was 29.3 years (SD 12.6) with no significant differences between men and women. There were no significant differences between the number of men and women diagnosed over the different decades or in the mean age at diagnosis. Female gender was significantly associated with the presence of oral ulcers (29.2% vs. 13.3%, p < 0.05) and Ig M ACA (9.9% vs. 0%, p < 0.05). There were no significant differences in the comparison of other variables. With respect to outcome, although renal failure and death were higher in females (6.8% vs. 4.4% and 13.2% vs. 6.6% respectively), no statistically significant differences were found. Cardiovascular disease was the commonest cause of death in men. CONCLUSION: Over this thirty year follow-up period, relatively few differences have emerged comparing the frequencies of clinical and serological features or outcome in male and female lupus patients.


Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , Adolescente , Adulto , Idoso , Autoanticorpos/sangue , Criança , Pré-Escolar , Estudos de Coortes , Etnicidade , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Londres/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
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