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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.
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
3.
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
4.
Arthritis Rheum ; 58(12): 3902-12, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19035499

RESUMO

OBJECTIVE: To identify in patients with Raynaud's phenomenon (RP) independent markers that predict progression to definite systemic sclerosis (SSc) and to determine in patients with progression to SSc the type and sequence of microvascular damage and its relationship to SSc-specific autoantibodies. METHODS: Consecutive patients referred for evaluation of RP who had no definite connective tissue disease were evaluated for microvascular damage by nailfold capillary microscopy (NCM) and for anticentromere (anti-CENP-B), anti-Th/To, anti-topoisomerase I, and anti-RNA polymerase III (anti-RNAP III) autoantibodies by specific assays. Patients were studied prospectively. RESULTS: Of the 586 patients who were followed up for 3,197 person-years, 74 (12.6%) developed definite SSc. A characteristic sequence of microvascular damage was identified, starting with enlarged capillaries, followed by capillary loss, and then by capillary telangiectases. Definite SSc was diagnosed in close temporal relationship to capillary loss. Enlarged capillaries, capillary loss, and SSc-specific autoantibodies independently predicted definite SSc. Anti-CENP-B and anti-Th/To antibodies predicted enlarged capillaries; these autoantibodies and anti-RNAP III predicted capillary loss. Each autoantibody was associated with a distinct time course of microvascular damage. At followup, 79.5% of patients with 1 of these autoantibodies and abnormal findings on NCM at baseline had developed definite SSc. Patients with both baseline predictors were 60 times more likely to develop definite SSc. The data validated the proposed criteria for early SSc. CONCLUSION: In RP evolving to definite SSc, microvascular damage is dynamic and sequential, while SSc-specific autoantibodies are associated with the course and type of capillary abnormalities. Abnormal findings on NCM at baseline together with an SSc-specific autoantibody indicate a very high probability of developing definite SSc, whereas their absence rules out this outcome.


Assuntos
Autoanticorpos/sangue , Microvasos/imunologia , Doença de Raynaud/imunologia , Doença de Raynaud/patologia , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Adulto , Especificidade de Anticorpos , Árvores de Decisões , Progressão da Doença , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Incidência , Masculino , Microvasos/patologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Doença de Raynaud/classificação , Doença de Raynaud/epidemiologia , Escleroderma Sistêmico/classificação , Escleroderma Sistêmico/epidemiologia , Estudos Soroepidemiológicos , Adulto Jovem
5.
Arthritis Rheum ; 57(1): 64-70, 2007 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-17266095

RESUMO

OBJECTIVE: We previously reported that patients with systemic lupus erythematosus (SLE) in the US incurred approximately 19% and 12% higher direct medical costs than patients in Canada and the UK, respectively, without experiencing superior outcomes expressed as disease damage or quality of life. In the present study, we compared cumulative indirect costs over 4 years in these patients. METHODS: A total of 715 patients with SLE (269 US, 231 Canada, 215 UK) were surveyed semiannually for 4 years on employment status and time lost from labor and nonlabor market activities. Cross-country comparisons of indirect costs were performed. RESULTS: In the US, Canada, and the UK, mean 4-year cumulative indirect costs (95% confidence interval [95% CI]) due to diminished labor market activity were $56,745 ($49,919, $63,571), $38,642 ($32,785, $44,500), and $42,213 ($35,859, $48,567), respectively, and cumulative indirect costs due to diminished nonlabor market activity were $5,249 ($2,766, $7,732), $5,455 ($3,290, $7,620), and $8,572 ($5,626, $11,518), respectively. Regression results showed that cumulative indirect costs (95% CI) due to diminished labor market activity in the US were $6,750 ($580, $12,910) greater than in Canada and $10,430 ($4,050, $16,800) greater than in the UK. Indirect costs due to diminished nonlabor market activity in the US were $280 (-$2,950, $3,520) less than in Canada and $2,010 (-$1,490, $5,510) less than in the UK, both results insignificant due to wide CIs. CONCLUSION: Despite American patients incurring greater direct medical costs than Canadian and British patients, they do not experience superior health outcomes in terms of less productivity loss in either labor market or nonlabor market activities.


Assuntos
Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/economia , Canadá , Eficiência , Humanos , Análise de Regressão , Fatores de Tempo , Reino Unido , Estados Unidos
6.
Medicine (Baltimore) ; 84(4): 231-49, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16010208

RESUMO

Our objective was to improve the currently imperfect classifications of idiopathic inflammatory myopathies (IIM). In clinical practice, overlap features are common in IIM. This provided a rationale for positioning overlap clinical features at the core of a new classification system. We conducted a longitudinal study of 100 consecutive adult French Canadian patients with IIM. Clinical and laboratory data were obtained by retrospective chart review. Sera were analyzed for autoantibodies (aAbs) by protein A-assisted immunoprecipitation and double immunodiffusion. Overlap aAbs encompassed aAbs to synthetases, systemic sclerosis-associated aAbs, anti-signal recognition particle (SRP) and anti-nucleoporins. Patients were classified both at IIM diagnosis, based on data at presentation, and at the end of follow-up, based on cumulative findings. Three classifications were used: 1) the Bohan and Peter original classification, 2) a new version of that classification as modified by us, and 3) a novel clinicoserologic classification. As investigators were blinded to aAb results, the modified classification is strictly a clinical classification. Its core concept is the attribution of diagnostic significance to the presence of overlap features, that is, their presence resulted in a diagnosis of overlap myositis (OM). This approach allowed direct comparison with the original Bohan and Peter classification. By integrating aAb results to the modified classification, we also defined the clinicoserologic classification, which allowed to examine the added value of aAbs to diagnostic, therapeutic and prognostic stratification. Whereas polymyositis (PM) was the most common IIM according to the original classification, accounting for 45% of the cohort at diagnosis, its frequency fell to 14% with the modified classification. Conversely, while the frequency of myositis associated with connective tissue disease was 24% according to the original classification, the frequency of OM was 60% when using the modified classification. At last follow-up, the frequency of PM fell further to only 9%, while the frequency of OM rose to 67%. Systemic sclerosis was the most common connective tissue disease associated with IIM, accounting for 42.6% of OM patients and 29% of the cohort. The frequencies of overlap aAbs in the cohort and in OM patients were 48% and 70.5% (n =48/68), respectively. The presence of overlap aAbs at IIM diagnosis identified additional OM patients unrecognized by the modified classification. The sensitivity of the modified classification for OM at diagnosis was 87%, suggesting that clinicians may rely on the modified classification for identification of most OM patients, while awaiting results of aAb assays. The new classifications predicted the response to prednisone and IIM course. Using stringent definitions, IIM was classified as responsive or refractory after an adequate initial corticosteroid therapy, and the disease course as monophasic or chronic after a single adequate trial of prednisone. PM was always chronic and was associated with the highest rate (50%) of refractoriness to initial corticosteroid treatment. Dermatomyositis was almost always chronic (92% rate); however, its responsiveness to initial corticosteroid treatment was high (87%). OM was almost always responsive to corticosteroids (89%-100% rates). When OM patients were divided according to aAb subsets, anti-synthetase, SRP, or nucleoporin aAbs were markers for chronic myositis, whereas aAbs to U1RNP, Pm-Scl, or Ku were markers for monophasic myositis. We conclude that the original Bohan and Peter classification should be abandoned as it leads to misclassification of patients. Much of IIM is composed of OM. The proposed modified and clinicoserologic classifications have diagnostic, prognostic, and therapeutic value.


Assuntos
Autoanticorpos/análise , Miosite/classificação , Adolescente , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Estudos de Coortes , Dermatomiosite/classificação , Dermatomiosite/imunologia , Feminino , Seguimentos , Humanos , Ligases/imunologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Miosite/imunologia , Complexo de Proteínas Formadoras de Poros Nucleares/imunologia , Polimiosite/classificação , Polimiosite/imunologia , Prednisona/uso terapêutico , Quebeque , Estudos Retrospectivos , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/imunologia , Partícula de Reconhecimento de Sinal/imunologia , Método Simples-Cego , Síndrome , Resultado do Tratamento
7.
J Rheumatol ; 30(5): 1011-6, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12734897

RESUMO

OBJECTIVE: We investigated whether brief supportive-expressive group psychotherapy might reduce illness-induced interference with valued activities and interests (i.e., illness intrusiveness) among women with systemic lupus erythematosus (SLE) in relation to 3 life domains: (1) relationships and personal development (family relationships, other social relationships, self-expression), (2) intimacy (relationship with spouse, sex life), and/or (3) instrumental life (work, finances, active recreation). METHODS: Women with SLE recruited from 9 rheumatology centers were randomly assigned to receive either usual care (n = 66) or a 12 week brief supportive-expressive group psychotherapy followed by 3 monthly booster sessions (n = 58). Standard instruments assessed disease activity and damage, illness intrusiveness, and psychological distress at 4 measurement occasions: (1) pretreatment, (2) posttreatment, (3) 6 month followup, and (4) 12 month followup. RESULTS: Analysis of covariance, controlling for disease activity and household income, indicated that women who received brief supportive-expressive group psychotherapy experienced significant reductions in illness intrusiveness for 2 of 3 domains: (1) relationships and personal development and (2) intimacy. Benefits were evident at 6 and 12 month followups. CONCLUSION: Brief supportive-expressive group psychotherapy facilitates adaptation to SLE by assisting women in reducing illness-induced disruptions into important domains of life experience.


Assuntos
Lúpus Eritematoso Sistêmico/psicologia , Lúpus Eritematoso Sistêmico/terapia , Psicoterapia de Grupo , Adaptação Psicológica , Adulto , Sintomas Afetivos , Doença Crônica , Feminino , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Comportamento Social
8.
Ann Behav Med ; 24(2): 88-99, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12054324

RESUMO

OBJECTIVE: To evaluate the effect of Brief Supportive-Expressive Group Psychotherapy as an adjunct to standard medical care in reducing psychological distress, medical symptoms, and health care costs and improving quality of life in women with systemic lupus erythematosus (SLE). METHODS: A randomized clinical trial was conducted with 133 SLE female patients from 9 clinics across Canada. Clinical and psychosocial measures were taken at baseline, posttreatment, and 6 and 12 months posttreatment. Outcomes assessed were psychological distress, quality of life, disease activity, health service utilization, and diminished productivity. RESULTS: Intention-to-treat analyses revealed that there were no clinically important group differences on any of the outcome measures. CONCLUSION: Although both groups improved over time on several measures (e.g., decreases in psychological distress, stress, and emotion-oriented coping), these changes could not be attributed to the psychotherapeutic intervention. Thus, evidence does not support the referral of these patients to this type of intervention.


Assuntos
Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/terapia , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/psicologia , Psicoterapia de Grupo/métodos , Adaptação Psicológica , Adulto , Feminino , Hospitalização , Humanos , Tempo de Internação , Lúpus Eritematoso Sistêmico/reabilitação , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Apoio Social , Estados Unidos
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