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1.
Arthritis Res Ther ; 22(1): 5, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915059

RESUMO

OBJECTIVE: To describe successful therapeutic strategies in statin-induced anti-HMGCR myopathy. METHODS: Retrospective data from a cohort of 55 patients with statin-induced anti-HMGCR myopathy, sequentially stratified by the presence of proximal weakness, early remission, and corticosteroid and IVIG use at treatment induction, were analyzed for optimal successful induction and maintenance of remission strategies. RESULTS: A total of 14 patients achieved remission with a corticosteroid-free induction strategy (25%). In 41 patients treated with corticosteroids, only 4 patients (10%) failed an initial triple steroid/IVIG/steroid-sparing immunosuppressant (SSI) induction strategy. Delay in treatment initiation was independently associated with lower odds of successful maintenance with immunosuppressant monotherapy (OR 0.92, 95% CI 0.85 to 0.97, P = 0.015). While 22 patients (40%) presented with normal strength, only 9 had normal strength at initiation of treatment. CONCLUSION: While corticosteroid-free treatment of anti-HMGCR myopathy is now a safe option in selected cases, initial triple steroid/IVIG/SSI was very efficacious in induction. Delays in treatment initiation and, as a corollary, delays in achieving remission decrease the odds of achieving successful maintenance with an SSI alone. Avoiding such delays, most notably in patients with normal strength, may reset the natural history of anti-HMGCR myopathy from a refractory entity to a treatable disease.

2.
Arthritis Care Res (Hoboken) ; 71(12): 1647-1652, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29693320

RESUMO

OBJECTIVE: Systemic lupus erythematosus (SLE) predominantly affects women. Clinical phenotype and outcomes in SLE may vary by sex and are further complicated by unique concerns that are dependent upon sex-defined roles. We aimed to describe sex differences in disease-specific quality of life (QoL) assessment scores using the Lupus Patient-Reported Outcome (LupusPRO) tool in a large international study. METHODS: Cross-sectional data from 1,803 patients with SLE on demographics, self-identified sex status, LupusPRO, and disease activity were analyzed. The LupusPRO tool has 2 constructs: health-related QoL (HRQoL) and non-HRQoL. Disease activity and damage were evaluated using the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, respectively. Nonparametric tests were used to compare QoL and disease activity by sex. RESULTS: A total of 122 men and 1,681 women with SLE participated. The mean age was similar by sex, but the damage scores were greater among men. Men fared worse on the non-HRQoL social support domain than women (P = 0.02). When comparing disease and QoL among men and women ages ≤45 years, men were found to have greater damage and worse social support than women. However, women fared significantly worse on lupus symptoms, cognition, and procreation domains with trends for worse functioning on physical health and pain-vitality domains. CONCLUSION: In the largest study of a diverse group of SLE patients, utilizing a disease-specific QoL tool, sex differences in QoL were observed on both HRQoL and non-HRQoL constructs. Although men performed worse in the social support domain, women (especially those in the reproductive age group) fared worse in other domains. These observations may assist physicians in appropriately addressing QoL issues in a sex-focused manner.

3.
J Rheumatol ; 45(10): 1426-1439, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30173152

RESUMO

OBJECTIVE: To develop recommendations for the assessment of people with systemic lupus erythematosus (SLE) in Canada. METHODS: Recommendations were developed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. The Canadian SLE Working Group (panel of Canadian rheumatologists and a patient representative from Canadian Arthritis Patient Alliance) was created. Questions for recommendation development were identified based on the results of a previous survey of SLE practice patterns of members of the Canadian Rheumatology Association. Systematic literature reviews of randomized trials and observational studies were conducted. Evidence to Decision tables were prepared and presented to the panel at 2 face-to-face meetings and online. RESULTS: There are 15 recommendations for assessing and monitoring SLE, with varying applicability to adult and pediatric patients. Three recommendations focus on diagnosis, disease activity, and damage assessment, suggesting the use of a validated disease activity score per visit and annual damage score. Strong recommendations were made for cardiovascular risk assessment and measuring anti-Ro and anti-La antibodies in the peripartum period and conditional recommendations for osteoporosis and osteonecrosis. Two conditional recommendations were made for peripartum assessments, 1 for cervical cancer screening and 2 for hepatitis B and C screening. A strong recommendation was made for annual influenza vaccination. CONCLUSION: These are considered the first guidelines using the GRADE method for the monitoring of SLE. Existing evidence is largely of low to moderate quality, resulting in more conditional than strong recommendations. Additional rigorous studies and special attention to pediatric SLE populations and patient preferences are needed.


Assuntos
Diretrizes para o Planejamento em Saúde , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapia , Programas de Rastreamento , Adulto , Canadá , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Criança , Feminino , Pessoal de Saúde , Hepatite C/diagnóstico , Hepatite C/etiologia , Humanos , /etiologia , Lúpus Eritematoso Sistêmico/complicações , Masculino , Osteonecrose/diagnóstico , Osteonecrose/etiologia , Osteoporose/diagnóstico , Osteoporose/etiologia , Período Periparto/sangue , Gravidez , Reumatologistas , Medição de Risco , Índice de Gravidade de Doença , Revisão Sistemática como Assunto , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/etiologia , Vacinação
4.
J Rheumatol ; 45(10): 1462-1476, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29961688

RESUMO

OBJECTIVE: Nontraumatic osteonecrosis (ON) is a well-recognized complication causing disability and affecting quality of life in patients with systemic lupus erythematosus (SLE). The aim of this study was to identify the risk factors for ON, and to identify the minimal investigation(s) needed to optimally monitor the risk of ON in patients with SLE. METHODS: A systematic review was conducted using MEDLINE and EMBASE. These databases were searched up to January 2016 using the Medical Subject Heading (MeSH) terms "Osteonecrosis," "Systemic lupus erythematosus," and synonymous text words. Randomized controlled trials, case control, cohort, and cross-sectional studies were included. Risk factors for ON in patients with SLE were compiled. The quality of each study was assessed using the Newcastle-Ottawa scale for nonrandomized studies. The quality of evidence of each risk factor was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation method. RESULTS: Of the 545 references yielded, 50 met inclusion criteria. Corticosteroid (CS) use may be strongly associated with ON in patients with SLE. Other clinical variables were moderately associated, including hypertension, serositis, renal disease, vasculitis, arthritis, and central nervous system disease. However, the evidence was low to very low in quality. CONCLUSION: Based on the best evidence available, CS use may be strongly associated with ON in patients with SLE. Results of this review were considered in the development of recommendations for the diagnosis and monitoring of patients with SLE in Canada and will guide clinicians in their assessment of these patients.


Assuntos
Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Osteonecrose/etiologia , Artrite/complicações , Canadá , Doenças do Sistema Nervoso Central/complicações , Humanos , Hipertensão/complicações , Nefropatias/complicações , Qualidade de Vida , Fatores de Risco , Serosite/complicações , Vasculite/complicações
5.
Medicine (Baltimore) ; 96(3): e5694, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28099331

RESUMO

The general aim of this study was to evaluate the disease spectrum in patients presenting with a pure polymyositis (pPM) phenotype. Specific objectives were to characterize clinical features, autoantibodies (aAbs), and membrane attack complex (MAC) in muscle biopsies of patients with treatment-responsive, statin-exposed necrotizing autoimmune myositis (NAM). Patients from the Centre hospitalier de l'Université de Montréal autoimmune myositis (AIM) Cohort with a pPM phenotype, response to immunosuppression, and follow-up ≥3 years were included. Of 17 consecutive patients with pPM, 14 patients had a NAM, of whom 12 were previously exposed to atorvastatin (mean 38.8 months). These 12 patients were therefore suspected of atorvastatin-induced AIM (atorAIM) and selected for study. All had aAbs to 3-hydroxy-3-methylglutaryl coenzyme A reductase, and none had overlap aAbs, aAbs to signal recognition particle, or cancer. Three stages of myopathy were recognized: stage 1 (isolated serum creatine kinase [CK] elevation), stage 2 (CK elevation, normal strength, and abnormal electromyogram [EMG]), and stage 3 (CK elevation, proximal weakness, and abnormal EMG). At diagnosis, 10/12 (83%) patients had stage 3 myopathy (mean CK elevation: 7247 U/L). The presenting mode was stage 1 in 6 patients (50%) (mean CK elevation: 1540 U/L), all of whom progressed to stage 3 (mean delay: 37 months) despite atorvastatin discontinuation. MAC deposition was observed in all muscle biopsies (isolated sarcolemmal deposition on non-necrotic fibers, isolated granular deposition on endomysial capillaries, or mixed pattern). Oral corticosteroids alone failed to normalize CKs and induce remission. Ten patients (83%) received intravenous immune globulin (IVIG) as part of an induction regimen. Of 10 patients with ≥1 year remission on stable maintenance therapy, IVIG was needed in 50%, either with methotrexate (MTX) monotherapy or combination immunosuppression. In the remaining patients, MTX monotherapy or combination therapy maintained remission without IVIG. AtorAIM emerged as the dominant entity in patients with a pPM phenotype and treatment-responsive myopathy. Isolated CK elevation was the mode of presentation of atorAIM. The new onset of isolated CK elevation on atorvastatin and persistent CK elevation on statin discontinuation should raise early suspicion for atorAIM. Statin-induced AIM should be included in the differential diagnosis of asymptomatic hyperCKemia. Three patterns of MAC deposition, while nonpathognomonic, were pathological clues to atorAIM. AtorAIM was uniformly corticosteroid resistant but responsive to IVIG as induction and maintenance therapy.


Assuntos
Atorvastatina/efeitos adversos , Doenças Autoimunes/induzido quimicamente , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Polimiosite/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/metabolismo , Doenças Autoimunes/patologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/imunologia , Quimioterapia de Indução , Estudos Longitudinais , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Polimiosite/tratamento farmacológico , Polimiosite/metabolismo , Polimiosite/patologia
6.
Curr Rheumatol Rev ; 13(2): 158-160, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27502238

RESUMO

The causal link between inherited complement deficiencies and systemic lupus erythematosus (SLE) has been well established, although it remains a rare cause of the disease. We present the case of three biological sisters with hereditary heterozygous C2 deficiency, but who differ widely in their clinical and serological manifestations. Patient 1 is 25 years old and was diagnosed with SLE at the age of 12. Further testing revealed positive ANA and anti-dsDNA, antiphospholipid syndrome (APS) and decreased C2, C3 and C4 levels. Patients 2 and 3 are 21-year-old dizygotic twins. Both have positive ANA and antiphospholipid (APL) antibodies, and decreased C2 and C4 levels. We present a case of familial heterozygous C2 deficiency with different disease phenotypes. The presence of positive APL antibodies in all 3 patients is significant, as this association has been rarely described. The variable clinical and serological manifestations among our patients further reflect the complex and multifactorial nature of SLE.


Assuntos
Complemento C2/deficiência , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Feminino , Humanos , Fenótipo , Irmãos , Adulto Jovem
7.
Arthritis Care Res (Hoboken) ; 67(1): 128-35, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24838943

RESUMO

OBJECTIVE: To estimate the early prevalence of various electrocardiographic (EKG) abnormalities in patients with systemic lupus erythematosus (SLE) and to evaluate possible associations between repolarization changes (increased corrected QT [QTc] and QT dispersion [QTd]) and clinical and laboratory variables, including the anti-Ro/SSA level and specificity (52 or 60 kd). METHODS: We studied adult SLE patients from 19 centers participating in the Systemic Lupus International Collaborating Clinics (SLICC) Inception Registry. Demographics, disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K]), disease damage (SLICC/American College of Rheumatology Damage Index [SDI]), and laboratory data from the baseline or first followup visit were assessed. Multivariate logistic and linear regression models were used to asses for any cross-sectional associations between anti-Ro/SSA and EKG repolarization abnormalities. RESULTS: For the 779 patients included, mean ± SD age was 35.2 ± 13.8 years, 88.4% were women, and mean ± SD disease duration was 10.5 ± 14.5 months. Mean ± SD SLEDAI-2K score was 5.4 ± 5.6 and mean ± SD SDI score was 0.5 ± 1.0. EKG abnormalities were frequent and included nonspecific ST-T changes (30.9%), possible left ventricular hypertrophy (5.4%), and supraventricular arrhythmias (1.3%). A QTc ≥440 msec was found in 15.3%, while a QTc ≥460 msec was found in 5.3%. Mean ± SD QTd was 34.2 ± 14.7 msec and QTd ≥40 msec was frequent (38.1%). Neither the specificity nor the level of anti-Ro/SSA was associated with QTc duration or QTd, although confidence intervals were wide. Total SDI was significantly associated with a QTc interval exceeding 440 msec (odds ratio 1.38 [95% confidence interval 1.06, 1.79]). CONCLUSION: A substantial proportion of patients with recent-onset SLE exhibited repolarization abnormalities, although severe abnormalities were rare.


Assuntos
Eletrocardiografia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Adulto , Estudos de Coortes , Estudos Transversais , Eletrocardiografia/métodos , Feminino , Seguimentos , Humanos , Internacionalidade , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Adulto Jovem
8.
Medicine (Baltimore) ; 93(24): 318-32, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25500701

RESUMO

Dermatomyositis (DM) is a major clinical subset of autoimmune myositis (AIM). The characteristic DM rash (Gottron papules, heliotrope rash) and perifascicular atrophy at skeletal muscle biopsy are regarded as specific features for this diagnosis. However, new concepts are challenging the current definition of DM. A modified Bohan and Peter classification of AIM was proposed in which the core concept was the inclusion of the diagnostic significance of overlap connective tissue disease features. In this clinical classification, a DM rash in association with myositis in the absence of overlap features indicates a diagnosis of pure DM. However, overlap features in association with myositis allow a diagnosis of overlap myositis (OM), irrespective of the presence or absence of the DM rash. Perifascicular atrophy may be present in both pure DM and OM. Recently, the presence of perifascicular atrophy in myositis without a DM rash was proposed as diagnostic of a novel entity, adermatopathic DM. We conducted the present study to evaluate these new concepts to further differentiate pure DM from OM.Using the modified Bohan and Peter classification, we performed a follow-up study of a longitudinal cohort of 100 consecutive adult French Canadian patients with AIM, including 44 patients with a DM phenotype, defined as a DM rash, and/or DM-type calcinosis, and/or the presence of perifascicular atrophy on muscle biopsy. A detailed evaluation was performed for overlap features, the extent and natural history of the DM rash, adermatopathic DM, DM-specific and overlap autoantibodies by protein A immunoprecipitation on coded serum samples, and associations with cancer and survival.Two distinct subsets were identified in patients with a DM phenotype: pure DM (n = 24) and OM with DM features, or OMDM (n = 20). In pure DM, the DM rash was a dominant finding. It was the first disease manifestation, was always present at the time of myositis diagnosis, and was associated with a high cutaneous score and chronicity. Concurrent heliotrope rash and Gottron papules (positive predictive value [PPV] 91%), as well as the V-sign and/or shawl sign (PPV 100%), were diagnostic of pure DM. Anti-Mi-2, anti-MJ, and anti-p155 autoantibodies were present in 50% of pure DM patients and were restricted to this subset (PPV 100%). Cancer was present in 21% of pure DM patients. The 15-year survival was excellent (92%).In contrast, in patients with OMDM, the first manifestation was proximal muscle weakness or other skeletal muscle-related complaints. The DM rash appeared at diagnosis or at follow-up, was associated with a low cutaneous extent score and was transient. Adermatopathic DM, which was absent in pure DM, was highly predictive (PPV 100%) of OMDM. Overlap autoantibodies (including anti-Jo-1, anti-PL-7, anti-PM-Scl, anti-U1RNP, and/or anti-U5-RNP) were found in 70% of OMDM patients. OMDM was not associated with cancer, but the 15-year survival was significantly decreased (65%).Perifascicular atrophy occurred as commonly in OMDM (n = 6/20, 30%) as in pure DM (n = 4/24, 17%) patients. These 6 OMDM patients had adermatopathic DM at myositis diagnosis, and only 1 of them developed a DM rash at follow-up, emphasizing the lack of specificity of perifascicular atrophy for pure DM.In conclusion, using the modified Bohan and Peter classification of AIM allowed identification of OMDM, a new clinical subset of OM. Furthermore, identification of OMDM allowed recognition of pure DM as a new entity that was distinct from OMDM or from OM without DM features. However, the absolute specificity of a DM rash and perifascicular muscle atrophy for the diagnosis of pure DM was lost. The distinctive clinical manifestations and autoantibody profiles presented are proposed as diagnostic criteria to differentiate pure DM from OMDM.


Assuntos
Dermatomiosite/diagnóstico , Miosite/diagnóstico , Adolescente , Adulto , Idoso , Atrofia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Dermatomiosite/patologia , Diagnóstico Diferencial , Exantema/diagnóstico , Exantema/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miosite/patologia , Pele/patologia , Adulto Jovem
10.
Clin Rheumatol ; 33(8): 1049-53, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24554383

RESUMO

Reactivation of latent tuberculosis (LTB) has been described with the use of anti-TNFs. Combined treatment of isoniazid (INH) and disease modifying antirheumatic drugs (DMARDs) can potentially increase the risk of hepatotoxicity. The goal of this study was to investigate the risk of hepatotoxicity in rheumatic patients taking INH while on DMARDs and/or biologics. We reviewed the Institut de Rhumatologie de Montréal database (Rhumadata®) for rheumatic patients with positive tuberculin skin test or quantiFERON who took INH between August 2001 and April 2011. Liver function tests (LFTs) were collected at baseline and during therapy, and LFTs up to 9 months prior to INH initiation were used as controls. Of 922 patients screened for LTB, 87 patients tested positive. During INH treatment, 75.9 % were taking DMARDs, 82.8 % were taking biologics. A total of 375 LFTs performed while on INH were compared to 211 available tests collected prior to INH therapy. Twenty-four percent of the patients had abnormal LFTs during INH compared to 12.1 % prior to INH (p = 0.0481). Most of these abnormalities were mild or transient, but 8 % (seven patients) had significant abnormalities leading to INH discontinuation. Among these patients, mean (min, max) was 241 (52, 617) for AST and 262 (92, 669) for ALT. Although the use of INH therapy in combination with DMARDs and/or biologics was generally well tolerated, the rate of LFT abnormalities was higher when patients were exposed to INH, and significant abnormalities were more frequent than reported in the INH literature. It is prudent to closely follow the LFTs of these patients.


Assuntos
Antirreumáticos/efeitos adversos , Antituberculosos/efeitos adversos , Produtos Biológicos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Isoniazida/efeitos adversos , Fígado/efeitos dos fármacos , Doenças Reumáticas/tratamento farmacológico , Adulto , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Produtos Biológicos/administração & dosagem , Produtos Biológicos/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Isoniazida/administração & dosagem , Isoniazida/uso terapêutico , Fígado/enzimologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade
11.
J Rheumatol ; 40(8): 1327-33, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23772082

RESUMO

OBJECTIVE: The LupusPRO, a disease-targeted patient-reported outcome measure, was developed and validated in US patients with systemic lupus erythematosus (SLE). We report the results of the cross-cultural validation study of the English version of the LupusPRO among patients in Canada with SLE. METHOD: The LupusPRO was administered to English-speaking Canadian patients with SLE. Demographic, clinical, and serological characteristics were obtained, and the Medical Outcomes Study Short Form-36 (SF-36) and LupusPRO were administered. Disease activity was ascertained using the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and the Lupus Foundation of America definition of flare (Yes/No). Damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Physician disease activity and damage assessments were also ascertained using visual analog scales. A mail-back LupusPRO form was completed within 2-3 days of the index visit. Items tested were internal consistency reliability (ICR), test-retest reliability (TRT), convergent and discriminant validity (against corresponding domains of the SF-36), criterion validity (against disease activity or health status), and known-groups validity. RESULTS: Participants were 123 Canadian patients with SLE (94% women); mean age was 47.7 (SD 14.8) years. The median (interquartile range) SELENA-SLEDAI and SDI were 4 (6) and 1 (3), respectively. The ICR of the LupusPRO domains ranged from 0.60 to 0.93, while the TRT range was 0.62-0.95. Measures observed were convergent and discriminant validity with corresponding domains of SF-36, criterion validity, and known-groups validity against disease activity, damage, and health status. Confirmatory factor analysis showed a good fit. CONCLUSION: The LupusPRO has fair psychometric properties among Canadian patients with SLE, and prospective studies to establish minimally important difference are continuing.


Assuntos
Cultura , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Autorrelato , Índice de Gravidade de Doença , Adulto , Canadá/epidemiologia , Feminino , Humanos , Linguagem , Masculino , Pessoa de Meia-Idade , Psicometria/métodos , Qualidade de Vida , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Traduções
12.
Arthritis Care Res (Hoboken) ; 65(8): 1275-80, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23401335

RESUMO

OBJECTIVE: To examine the association between smoking and cutaneous involvement in systemic lupus erythematosus (SLE). METHODS: We analyzed data from a multicenter Canadian SLE cohort. Mucocutaneous involvement was recorded at the most recent visit using the Systemic Lupus Erythematosus Disease Activity Index 2000 Update (rash, alopecia, and oral ulcers), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (alopecia, extensive scarring, and skin ulceration), and the ACR revised criteria for SLE (malar rash, discoid rash, photosensitivity, and mucosal involvement). Multivariate logistic regression models were used to estimate the independent association between mucocutaneous involvement and cigarette smoking, age, sex, ethnicity, lupus duration, medications, and laboratory data. RESULTS: In our cohort of 1,346 patients (91.0% women), the mean ± SD age was 47.1 ± 14.3 years and the mean ± SD disease duration was 13.2 ± 10.0 years. In total, 41.2% of patients were ever smokers, 14.0% current smokers, and 27.1% past smokers. Active mucocutaneous manifestations occurred in 28.4% of patients; cutaneous damage occurred in 15.4%. Regarding the ACR criteria, malar rash was noted in 59.5%, discoid rash in 16.9%, and photosensitivity in 55.7% of patients. In the multivariate analysis, current smoking was associated with active SLE rash (odds ratio [OR] 1.63 [95% confidence interval (95% CI) 1.07, 2.48]). Having ever smoked was associated with ACR discoid rash (OR 2.36 [95% CI 1.69, 3.29]) and photosensitivity (OR 1.47 [95% CI 1.11, 1.95]), and with the ACR total cutaneous score (OR 1.50 [95% CI 1.22, 1.85]). We did not detect any associations between previous smoking and active cutaneous manifestations. No association was found between smoking and cutaneous damage or mucosal ulcers. No interaction was seen between smoking and antimalarials. CONCLUSION: Current smoking is associated with active SLE rash, and ever smoking with the ACR total cutaneous score. This provides additional motivation for smoking cessation in SLE.


Assuntos
Lúpus Eritematoso Sistêmico/patologia , Dermatopatias/etiologia , Pele/patologia , Fumar/efeitos adversos , Adulto , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade
13.
Arthritis Care Res (Hoboken) ; 63(7): 1031-7, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21452253

RESUMO

OBJECTIVE: To examine whether anti-Ro/SSA antibodies are associated with an increased risk of corrected QT (QTc) prolongation, and to study the stability of this relationship over time. METHODS: Patients fulfilling the American College of Rheumatology (ACR) criteria for systemic lupus erythematosus (SLE) were invited to undergo a 12-lead resting electrocardiogram (EKG) in the pilot phase of our project, performed between February 2002 and March 2005. The same study population was used to perform a second similar analysis with a larger sample between April 2005 and May 2007. Multivariate logistic regression models were fit to estimate the cross-sectional association between anti-Ro/SSA and other demographic and clinical variables on QTc prolongation. The other potentially associated factors examined included age, sex, disease duration, lupus activity (Systemic Lupus Erythematosus Disease Activity Index 2000 update), damage (Systemic Lupus International Collaborating Clinics/ACR Damage Index), potassium and magnesium levels, and medications with the potential to prolong the QTc interval. RESULTS: Cross-sectional analysis of the pilot data (n = 150 patients) showed an association of prolonged QTc with the presence of anti-Ro/SSA (adjusted odds ratio [OR] 12.6; 95% confidence interval [95% CI] 2.3, 70.7). In the second larger study (n = 278), the association was replicated, with a narrower 95% CI (adjusted OR 5.1; 95% CI 1.5, 17.4). In the 118 patients with 2 EKG assessments, the results were consistent over time. CONCLUSION: Anti-Ro/SSA was associated with QTc prolongation in both our pilot data and a larger SLE cohort sample. Patients positive for anti-Ro/SSA may benefit from EKG testing and appropriate counseling should be considered for those identified with QTc prolongation.


Assuntos
Anticorpos Antinucleares/imunologia , Bloqueio Cardíaco/fisiopatologia , Síndrome do QT Longo/fisiopatologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Adulto , Estudos Transversais , Eletrocardiografia , Feminino , Bloqueio Cardíaco/imunologia , Humanos , Síndrome do QT Longo/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade
15.
J Rheumatol ; 37(7): 1422-30, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20516029

RESUMO

OBJECTIVE: To develop recommendations for the use of methotrexate (MTX) in patients with rheumatoid arthritis. METHODS: Canadian rheumatologists who participated in the international 3e Initiative in Rheumatology (evidence, expertise, exchange) in 2007-2008 formulated 5 unique Canadian questions. A bibliographic team systematically reviewed the relevant literature on these 5 topics. An expert committee consisting of 26 rheumatologists from across Canada was convened, and a set of recommendations was proposed based on the results of systematic reviews combined with expert opinions using a nominal group consensus process. RESULTS: The 5 questions addressed drug interactions, predictors of response, strategies to reduce non-serious side effects, variables to assess clinical response, and incorporating patient preference into decision-making. The systematic review retrieved 93 pertinent articles; this evidence was presented to the expert committee during the interactive workshop. After extensive discussion and voting, a total of 9 recommendations were formulated: 2 on drug interactions, 1 on predictors of response, 2 on strategies to reduce non-serious side effects, 3 on variables to assess clinical response, and 1 on incorporating patient preferences into decision-making. The level of evidence and the strength of recommendations are reported. Agreement among panelists ranged from 85% to 100%. CONCLUSION: Nine recommendations pertaining to the use of MTX in daily practice were developed using an evidence-based approach followed by expert/physician consensus with high level of agreement.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Guias de Prática Clínica como Assunto , Antirreumáticos/efeitos adversos , Canadá , Medicina Baseada em Evidências , Doenças Hematológicas/induzido quimicamente , Humanos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Metotrexato/efeitos adversos , Preferência do Paciente , Reumatologia/normas
16.
J Rheumatol ; 37(7): 1416-21, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20436072

RESUMO

OBJECTIVE: Patients with rheumatoid arthritis (RA) often have comorbidities that require multiple medications. Several of these medications may alter the efficacy or increase the toxicity of methotrexate (MTX). The purpose of our study was to determine which drugs used in combination with MTX (excluding disease modifying antirheumatic drugs, folic and folinic acid, corticosteroids, and biologic agents) enhance side effects or toxicity of MTX or lower its efficacy. METHODS: A systematic literature search was performed with Medline, Embase, Cochrane Register and Database, and abstracts from the 2006/2007 annual congresses of the American College of Rheumatology and the European League Against Rheumatism. A manual search of the citation lists of retrieved publications was performed. RESULTS: Of the 1172 articles identified, 67 were included: 21 pharmacokinetics studies, 5 observational studies, and 78 case reports. Most medications do not significantly affect the pharmacokinetics profile of MTX. Among the clinical studies, cytopenia and elevation of liver enzymes were the main reported toxicities. The use of trimethoprim-sulfamethoxazole (TMP-SMX) was mentioned as a risk factor for developing cytopenia in one observational study and in 17 case reports. Thirty case reports of cytopenia were attributed to the use of concomitant nonsteroidal antiinflammatory drugs, including acetylsalicylic acid. Two studies described mild abnormalities of liver enzymes with the use of isoniazid, and one study with the use of high-dose ASA. CONCLUSION: Based on the published literature, MTX has limited drug interactions, with the exception of TMP-SMX and high-dose ASA, which can exacerbate toxicity of MTX. The clinical significance of these interactions has not been substantiated by extensive clinical observations.


Assuntos
Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Interações de Medicamentos , Doenças Hematológicas/induzido quimicamente , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Ensaios Clínicos como Assunto , Bases de Dados Factuais , Humanos , Fatores de Risco , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
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