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Espondiloartrite Axial , Aprendizado Profundo , Sacroileíte , Espondilartrite , Algoritmos , Humanos , Imageamento por Ressonância Magnética/métodos , Articulação Sacroilíaca/diagnóstico por imagem , Articulação Sacroilíaca/patologia , Sacroileíte/diagnóstico por imagem , Sacroileíte/patologia , Espondilartrite/complicações , Espondilartrite/diagnóstico por imagem , Espondilartrite/patologiaRESUMO
BACKGROUND: Ankylosing spondylitis (AS) affects one in 200 individuals and is usually diagnosed many years after onset of symptoms. Chronic back pain is common and recognition of early disease requires clinical experience and a high index of suspicion. Further, inflammatory markers are not invariably elevated and radiographic changes are often late findings. OBJECTIVE: The objective of this review is to address AS and the recently defined disorder of non-radiographic axial spondyloarthritis. The latter is a common early presentation of AS, before the development of radiographic sacroiliitis, and will evolve into typical AS in 50% of patients. DISCUSSION: MRI may be particularly useful in evaluating early disease, although chronic changes of sacroiliitis are better seen on plain X-rays. Nonsteroidal anti-inflammatory drugs (NSAIDs) are first-line therapy and recent studies suggest that regular use among patients with AS slows radiographic progression. Tumour necrosis inhibitor therapy has strikingly improved quality of life for the more than two-thirds of AS patients with an inadequate response to NSAIDs.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Biomarcadores/análise , Imageamento por Ressonância Magnética/métodos , Espondilite Anquilosante , Progressão da Doença , Humanos , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/metabolismoRESUMO
BACKGROUND: The understanding of non-radiographic axial spondyloarthritis (nr-axSpA) has accelerated over the last decade, producing a number of practice-changing developments. Diagnosis is challenging. No diagnostic criteria exist, no single finding is diagnostic, and other causes of back pain may act as confounders. AIM: To update and expand the 2014 consensus statement on the investigation and management of non-radiographic axial spondyloarthritis (nr-axSpA). METHODS: We created search questions based on our previous statements and four new topics then searched the MEDLINE and Cochrane databases. We assessed relevant publications by full-text review and rated their level of evidence using the GRADE system. We compiled a GRADE evidence summary then produced and voted on consensus statements. RESULTS: We identified 5145 relevant publications, full-text reviewed 504, and included 176 in the evidence summary. We developed and voted on 22 consensus statements. All had high agreement. Diagnosis of nr-axSpA should be made by experienced clinicians, considering clinical features of spondyloarthritis, blood tests, and imaging. History and examination should also assess alternative causes of back pain and related conditions including non-specific back pain and fibromyalgia. Initial investigations should include CRP, HLA-B27, and AP pelvic radiography. Further imaging by T1 and STIR MRI of the sacroiliac joints is useful if radiography does not show definite changes. MRI provides moderate-to-high sensitivity and high specificity for nr-axSpA. Acute signs of sacroiliitis on MRI are not specific and have been observed in the absence of spondyloarthritis. Initial management should involve NSAIDs and a regular exercise program, while TNF and IL-17 inhibitors can be used for high disease activity unresponsive to these interventions. Goals of treatment include improving the frequent impairment of social and occupational function that occurs in nr-axSpA. CONCLUSIONS: We provide 22 evidence-based consensus statements to provide practical guidance in the assessment and management of nr-axSpA.
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STUDY OBJECTIVES: To investigate whether age at disease onset is a risk factor for pulmonary arterial hypertension (PAH) in scleroderma. SETTING: Scleroderma center. PATIENTS: Seven hundred nine consecutive scleroderma patients who underwent echocardiography. MEASUREMENTS: The risk of PAH associated with age at disease onset was modeled as both a continuous and categorical variable. Risk estimates were adjusted for sex, race, scleroderma subtype, disease duration, smoking status, FVC, anticentromere and antitopoisomerase I antibody status. RESULTS: Overall, 274 patients (38.6%), 272 patients by Doppler echocardiography and 2 patients by M-mode echocardiography, had PAH at baseline or during follow-up. There were 114 patients with mild PAH (right ventricular systolic pressure [RVSP], 36 to 45 mm Hg), 66 patients with moderate PAH (RVSP, 46 to 55 mm Hg), and 92 patients with severe PAH (RVSP > or =56 mm Hg). A 52% increase in risk of PAH was demonstrated for every 10 years of age at disease onset (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.31 to 1.76). In addition, there was a twofold greater risk of PAH (OR, 2.30; 95% CI, 1.32 to 3.99) for late-onset (age > or =60 years) vs earlier-onset (< 60 years) disease. These associations remained evident and were somewhat strengthened when the analyses were restricted to patients with moderate and severe PAH. CONCLUSIONS: We identified increasing age at scleroderma onset as a risk factor for PAH. Vigilance among these high-risk patients may provide an opportunity to intervene prior to development of irreversible pulmonary vascular disease.
Assuntos
Envelhecimento , Ecocardiografia , Hipertensão Pulmonar/etiologia , Escleroderma Sistêmico/complicações , Adolescente , Adulto , Idoso , Criança , Intervalos de Confiança , Feminino , Humanos , Hipertensão Pulmonar/classificação , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To understand the impact of ankylosing spondylitis (AS) on presenteeism and to explore its relationship to sick leave. METHODS: AS patients completed a questionnaire consisting of sociodemographics, disease characteristics, and work outcomes, including sick leave and presenteeism, assessed by the Work Limitations Questionnaire (WLQ). Associations between a broad range of explanatory variables with the WLQ and AS-related sick leave were assessed by zero-inflated negative binomial and zero-inflated Poisson regressions. RESULTS: Of 311 employed patients (204 men [65.6%]), 18% had sick leave in the past month. Limitations in meeting time management demands (33.7%), physical demands (30.2%), mental-interpersonal demands (20.2%), and output (19.0%) were noted. With the mean ± SD WLQ index score of 6.7 ± 5.9, the average decrease in work productivity attributable to health was 6.3%; an extra 7.1% of work hours would be needed to compensate for lost productivity. Helplessness, female sex, and impaired health-related quality of life (Ankylosing Spondylitis Quality of Life instrument [ASQoL]) were major contributors to the level of presenteeism (P < 0.01). At-work limitations (WLQ) and lower quality of life (ASQoL) were significantly associated with probability of sick leave, while the length of sick leave was strongly associated with lower educational level and helplessness (P < 0.01), and in some models, also with disease duration and country of residence (P < 0.05). CONCLUSION: AS hinders patients' work, mainly in time management and physical demand domains. The WLQ and ASQoL are able to identify patients who incur sick leave. Helplessness contributes independently to the level of presenteeism and the length of sick leave.
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Absenteísmo , Compreensão , Qualidade de Vida , Licença Médica/tendências , Espondilite Anquilosante/epidemiologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/psicologia , Inquéritos e QuestionáriosRESUMO
AIM: Non-radiographic axial spondyloarthritis (nr-axSpA) is axial inflammatory arthritis where plain radiographic damage is not evident. An unknown proportion of these patients will progress to ankylosing spondylitis (AS). The increasing recognition of nr-axSpA has been greatly assisted by the widespread use of magnetic resonance imaging. The aim of this article was to construct a set of consensus statements based on a literature review to guide investigation and promote best management of nr-axSpA. METHODS: A literature review using Medline was conducted covering the major investigation modalities and treatment options available. A group of rheumatologists and a radiologist with expertise in investigation and management of SpA reviewed the literature and formulated a set of consensus statements. The Grade system encompassing the level of evidence and strength of recommendation was used. The opinion of a patient with nr-axSpA and a nurse experienced in the care of SpA patients was also sought and included. RESULTS: The literature review found few studies specifically addressing nr-axSpA, or if these patients were included, their results were often not separately reported. Fourteen consensus statements covering investigation and management of nr-axSpA were formulated. The level of agreement was high and ranged from 8.1 to 9.8. Treatment recommendations vary little with established AS, but this is primarily due to the lack of available evidence on the specific treatment of nr-axSpA. CONCLUSION: The consensus statements aim to improve the diagnosis and management of nr-axSpA. We aim to raise awareness of this condition by the public and doctors and promote appropriate investigation and management.
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Imageamento por Ressonância Magnética/normas , Reumatologia/normas , Espondilartrite/diagnóstico , Espondilartrite/terapia , Consenso , Progressão da Doença , Medicina Baseada em Evidências/normas , Humanos , Valor Preditivo dos Testes , Radiografia , Espondilartrite/diagnóstico por imagem , Espondilartrite/enfermagem , Resultado do TratamentoRESUMO
An increase in reports of systemic lupus erythematosus (SLE) related to tumour necrosis factor inhibitor (TNFi) therapy has recently been highlighted. We report new-onset SLE in a 22-year-old woman after 13 months of infliximab for ankylosing spondylitis (AS). Lupus symptoms promptly resolved and serologic abnormalities improved after infliximab was ceased. A flare of AS symptoms after 2 months prompted cautious introduction of an alternative TNFi, etanercept. At 14 months follow-up, neither clinical nor serologic flare of lupus had occurred. To our knowledge, this is the third reported case of infliximab-related lupus that did not recur on switching to an alternative TNFi.
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Anticorpos Monoclonais/farmacologia , Imunoglobulina G/farmacologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Antirreumáticos/farmacologia , Autoimunidade , DNA/metabolismo , Etanercepte , Feminino , Humanos , Inflamação , Infliximab , Lúpus Eritematoso Sistêmico/sangue , Qualidade de Vida , Receptores do Fator de Necrose Tumoral , Espondilite Anquilosante/sangue , Fatores de TempoRESUMO
Tumour necrosis factor inhibitor (TNFi) therapy, either intravenous (IV) or subcutaneous (SQ), demonstrates similar efficacy in ankylosing spondylitis (AS). The objective of this study was to examine factors influencing patient preference of TNFi. Fifty-nine (79.7%) participants were male with mean age 43.9 years and disease duration of 22.0 years. Fifty-nine patients (79.7%) agreed with the statement 'My doctor gave me a choice and I made a decision based on my personal preference'. Patients commenced first on IV TNFi most commonly cited reduced frequency of injections (96.6%), administration by a trained professional (89.7%) and use of infusion time for leisure activities (86.2%). Patients commenced on SQ TNFi cited flexibility with timing of treatment (80%), shortened administration time (73.3%) and the convenience of home therapy (73.3%). Shared clinical decision-making between clinicians and patients may be desirable for AS patients commencing TNFi therapy.
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Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Antirreumáticos/uso terapêutico , Comunicação , Feminino , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Aims. To compare the baseline characteristics of a population-based cohort of patients with ankylosing spondylitis (AS) commencing biological therapy to the reported characteristics of bDMARD randomised controlled trials (RCTs) participants. Methods. Descriptive analysis of AS participants in the Australian Rheumatology Association Database (ARAD) who were commencing bDMARD therapy. Results. Up to December 2008, 389 patients with AS were enrolled in ARAD. 354 (91.0%) had taken bDMARDs at some time, and 198 (55.9%) completed their entry questionnaire prior to or within 6 months of commencing bDMARDs. 131 (66.1%) had at least one comorbid condition, and 24 (6.8%) had a previous malignancy (15 nonmelanoma skin, 4 melanoma, 2 prostate, 1 breast, cervix, and bowel). Compared with RCT participants, ARAD participants were older, had longer disease duration and higher baseline disease activity. Conclusions. AS patients commencing bDMARDs in routine care are significantly different to RCT participants and have significant baseline comorbidities.
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Prevalence of dietary complementary and alternative medicine (CAM) and consultation with a CAM practitioner was examined in a cross-sectional study of 75 AS patients. Seventy one of 75 (94.7%) study participants reported previous or current CAM use. Among these AS patients, 44 (72.1%) reported dietary CAM use and 27 (36.0%) were seeing a CAM practitioner at the time of study. Of 89 dietary CAM, 50 (56.4%) were perceived to be of slight or no benefit, and only 10 (11.2%) were initiated by a CAM practitioner. Compared with non-users, current dietary CAM users were more likely to be female (OR 6.5; 95% CI, 1.8-23.9). Patients attending a CAM practitioner were more likely to have university education (OR 5.7; 95% CI, 1.5-21.9) and higher BASDAI (OR 1.3; 95%CI, 1.0-1.7). Despite low rates of perceived benefit, dietary CAM use and CAM practitioner attendance is common among AS patients.
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Terapias Complementares/estatística & dados numéricos , Dietoterapia/estatística & dados numéricos , Espondilite Anquilosante/terapia , Acupuntura/estatística & dados numéricos , Adulto , Terapias Complementares/métodos , Estudos Transversais , Feminino , Homeopatia/estatística & dados numéricos , Humanos , Masculino , Massagem/estatística & dados numéricos , Pessoa de Meia-Idade , Prevalência , Encaminhamento e Consulta/estatística & dados numéricos , Classe SocialRESUMO
As part of the 3E program, we conducted a systematic literature review and gathered consensus from 23 practising Australian rheumatologists to develop guidelines for early identification of ankylosing spondylitis and specialist referral. In three rounds of break-out sessions followed by discussion and voting, the specialist panel addressed three questions related to diagnosis of ankylosing spondylitis: In individuals with back pain, what are the early clinical features that suggest ankylosing spondylitis? How useful is imaging in identifying early ankylosing spondylitis? Based on which clinical features should a general practitioner refer a patient to a rheumatologist for further evaluation? The panel agreed on six recommendations related to the three questions: 1a. Early clinical features to suggest ankylosing spondylitis include inflammatory back pain and age at symptom onset < 45 years. 1b. The absence of symptomatic response to an appropriate course of non-steroidal anti-inflammatory drugs makes the diagnosis of ankylosing spondylitis less likely. 1c. Raised inflammatory markers are supportive, but their absence does not rule out the diagnosis of ankylosing spondylitis. 2a. Despite low sensitivity to detect changes of early ankylosing spondylitis, plain radiographs of the pelvis and spine are appropriate initial imaging techniques. 2b. Magnetic resonance imaging is a useful imaging modality for detecting early changes of ankylosing spondylitis. 3. Individuals with inflammatory back pain should be referred to a rheumatologist for further evaluation. Effective dissemination and implementation of these recommendations are important to standardise the approach to early diagnosis of ankylosing spondylitis.
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Espondilite Anquilosante/diagnóstico , Austrália , Diagnóstico Precoce , Medicina Baseada em Evidências , HumanosRESUMO
OBJECTIVE: To determine risk factors for developing pulmonary hypertension (PH) in patients with scleroderma (SSc, systemic sclerosis). METHODS: We used a cohort of 1136 SSc patients using severe PH as the primary outcome in a natural history study. RESULTS: Among 361 individuals with no initial echocardiographic PH, 92 (26.0%) developed mild-moderate PH and 48 (13.6%) severe PH. Patients developing severe PH had lower initial DLCO (48.8% of predicted) than those who did not develop PH (56.8% of predicted). Patients with mild-moderate PH had a 17% probability of progressing to severe PH, and 15.6% probability of regressing to no PH. Individuals with limited disease, mild-moderate PH, and age > or= 47 years at diagnosis had a 27.3% probability of developing severe PH, compared to 8.5% in individuals with diffuse disease, no evidence of PH, and age < 47 years at diagnosis. Longitudinal regression models estimated that individuals with limited disease, mild-moderate PH, and DLCO < 50% predicted had an age-adjusted odds ratio of 8.6 of developing severe PH within 2 years compared to individuals without these risk factors. CONCLUSION: Development of severe PH is uncommon in certain subgroups of SSc patients. Risk factors for progression of PH include older age, limited skin disease, and elevated pulmonary artery pressures at the time of initial evaluation.
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Hipertensão Pulmonar/etiologia , Escleroderma Sistêmico/complicações , Adulto , Estudos de Coortes , Comorbidade , Progressão da Doença , Eletrocardiografia , Feminino , Hospitais Universitários , Humanos , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/fisiopatologia , Masculino , Maryland/epidemiologia , Pessoa de Meia-Idade , Testes de Função Respiratória , Fatores de Risco , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/fisiopatologiaRESUMO
OBJECTIVE: Lung transplantation is a viable, life-saving intervention for several primary pulmonary disorders complicated by severe lung dysfunction. This study was undertaken to evaluate whether patients with systemic sclerosis (scleroderma), a systemic autoimmune rheumatic disorder, would receive similar benefit from this intervention. METHODS: Survival following lung transplantation was examined at 2 university medical centers among 29 patients with scleroderma as compared with 70 patients with idiopathic pulmonary fibrosis (IPF) and 38 with idiopathic pulmonary arterial hypertension (IPAH), the latter groups representing pathologically related primary pulmonary disorders. The end point was death from any cause. Risk of mortality in patients with scleroderma was compared with that in patients with IPF or IPAH, with adjustment for demographic and clinical parameters. RESULTS: During 2 years of followup, 11 patients with scleroderma (38%), 23 with IPF (33%), and 14 with IPAH (37%) died. Cumulative survival at 6 months posttransplantation was 69% in the scleroderma group compared with 80% in the IPF group (log-rank P = 0.21) and 79% in the IPAH group (P = 0.38). The estimated risk of mortality at 6 months was increased in patients with scleroderma compared with those with IPF (relative risk [RR] 1.70, 95% confidence interval [95% CI] 0.74-3.93) and those with IPAH (RR 1.52, 95% CI 0.59-3.96), but the differences were not statistically significant. Over the following 18 months, there was convergence in the survival rates such that cumulative survival at 2 years was comparable, at approximately 64%, among all 3 groups. CONCLUSION: Patients with scleroderma who are recipients of lung transplantation experience similar rates of survival 2 years after the procedure compared with those with IPF or IPAH. Lung transplantation may represent a viable therapeutic option to consider for patients with end-stage lung disease due to scleroderma.
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Hipertensão Pulmonar/cirurgia , Transplante de Pulmão , Artéria Pulmonar/patologia , Fibrose Pulmonar/cirurgia , Escleroderma Sistêmico/cirurgia , Adulto , Feminino , Hospitais Universitários , Humanos , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/patologia , Masculino , Maryland/epidemiologia , Pessoa de Meia-Idade , Pennsylvania/epidemiologia , Fibrose Pulmonar/mortalidade , Fibrose Pulmonar/patologia , Estudos Retrospectivos , Escleroderma Sistêmico/mortalidade , Taxa de SobrevidaRESUMO
Increasing evidence suggests that the vasculopathy of scleroderma is mediated by a number of soluble factors and involves a complex interaction between endothelial cells, smooth muscle cells, extracellular matrix, intravascular coagulation factors, and circulating cells. Novel therapeutic approaches beyond vasodilator therapy are being developed by recognizing important molecular pathways involved in scleroderma vascular disease. The success of this strategy is most evident in pulmonary hypertension, an often fatal complication of scleroderma. In this article, the authors explore therapies for scleroderma that target endothelial cells, smooth muscle cells, reactive oxygen species, and circulating blood cells. The authors highlight clinical trials that have investigated the role of prostacyclin (and its analogues) and bosentan in managing scleroderma-related pulmonary hypertension. Finally, the authors look at the potential role of biomarkers as surrogate indicators of active vascular disease in scleroderma.
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Epoprostenol/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Escleroderma Sistêmico/tratamento farmacológico , Sulfonamidas/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Biomarcadores , Bosentana , Ensaios Clínicos como Assunto , Endotelina-1/fisiologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiopatologia , Espécies Reativas de Oxigênio , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/fisiopatologiaRESUMO
OBJECTIVE: To examine whether autoantibodies recognizing granzyme B (GB)-cleaved autoantigens are associated with ischemic digital loss (IDL) in limited systemic sclerosis (SSc). METHODS: Fifteen of 19 patients with limited SSc and IDL were matched by age, sex, race, and duration of disease to controls with limited SSc but without IDL. The sera were used to immunoblot HeLa cell lysates and chromosome preparations that had been incubated in vitro in the absence or presence of GB. Anticentromere antibodies (ACAs) were assayed by immunofluorescence and immunoprecipitation of in vitro-translated centromere proteins (CENP-B and CENP-C). Immunoprecipitation of GB-cleaved CENPs was also performed. RESULTS: GB-cleaved autoantigens were immunoblotted by 16 of 19 IDL sera (84.2%) compared with 6 of 15 non-IDL sera (40.0%) (odds ratio 8.0, 95% confidence interval 1.6-40.0). This association persisted after adjustment for ACA status. Furthermore, the presence of antibodies to centromere proteins as well as to GB-cleaved antigens was highly specific for IDL, occurring in 12 of 19 IDL patients (63.2%) and in none of 15 controls (P < 0.0001). An identical 60-kd GB-generated fragment was recognized by 5 of 16 IDL sera (31.3%) and was demonstrated to arise through GB-mediated cleavage of CENP-C. GB-cleaved CENP-C fragments were recognized preferentially over the intact CENP-C molecule by antibodies from patients with IDL. CONCLUSION: The striking recognition of GB-generated autoantigen fragments by sera from patients with limited SSc and IDL constitutes the first in vivo evidence that antibodies against GB-generated centromeric peptide fragments identify a distinct clinical subset.