RESUMO
OBJECTIVE: To assess predictors of subclinical RA-associated interstitial lung disease (RA-ILD) using quantitative lung densitometry (qLD). METHODS: RA patients underwent multi-detector row CT scanning at baseline and after an average of 39 months. Scans were analysed with qLD for the percentage of lung parenchyma with high attenuation areas (%HAA: the percentage of voxels of -600 to -250 Hounsfield units). Additionally, a pulmonary radiologist calculated an expert radiologist scoring (ERS) for RA-ILD features. Generalized linear models were used to identify indicators of baseline %HAA and predictors of %HAA change. RESULTS: Baseline %HAA was assessed in 193 RA patients and 106 had repeat qLD assessment. %HAA was correlated with ERS (Spearman's rho = 0.261; P < 0.001). Significant indicators of high baseline %HAA (>10% of lung parenchyma with high attenuation) included female sex, higher pack-years of smoking, higher BMI and anti-CCP ≥200 units, collectively contributing an area under the receiver operator curve of 0.88 (95% CI 0.81, 0.95). Predictors of %HAA increase, occurring in 49% with repeat qLD, included higher baseline %HAA, presence of mucin 5B (MUC5B) minor allele and absence of HLA-DRB1 shared epitope (area under the receiver operator curve = 0.69; 95% CI 0.58, 0.79). The association of the MUC5B minor allele with %HAA change was higher among men and those with higher cumulative smoking. Within the group with increased %HAA, anti-CCP level was significantly associated with a greater increase in %HAA. CONCLUSIONS: %HAA, assessed with qLD, was linked to several known risk factors for RA-ILD and may represent a more quantitative method to identify RA-ILD and track progression than expert radiologist interpretation.
Assuntos
Artrite Reumatoide , Doenças Pulmonares Intersticiais , Anticorpos Antiproteína Citrulinada , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico por imagem , Densitometria , Feminino , Humanos , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/etiologia , MasculinoRESUMO
BACKGROUND/OBJECTIVE: Patients classified as interstitial pneumonia with autoimmune features (IPAF) have interstitial lung disease (ILD) and features of autoimmunity but do not fulfill criteria for connective tissue diseases (CTDs). Our goal was to identify patients classifiable as IPAF, CTD-ILD, and idiopathic pulmonary fibrosis (IPF) from a preexisting pulmonary cohort and evaluate the prognosis of patients with IPAF. METHODS: We reviewed the medical records of 456 patients from a single-center pulmonary ILD cohort whose diagnoses were previously established by a multidisciplinary panel that did not include rheumatologists. We reclassified patients as IPAF, CTD-ILD, or IPF. We compared transplant-free survival using Kaplan-Meier methods and identified prognostic factors using Cox models. RESULTS: We identified 60 patients with IPAF, 113 with CTD-ILD, and 126 with IPF. Transplant-free survival of IPAF was not statistically significantly different from that of CTD-ILD or IPF. Among IPAF patients, male sex (hazard ratio, 4.58 [1.77-11.87]) was independently associated with worse transplant-free survival. During follow-up, only 10% of IPAF patients were diagnosed with CTD-ILD, most commonly antisynthetase syndrome. CONCLUSION: Despite similar clinical characteristics, most patients with IPAF did not progress to CTD-ILD; those who did often developed antisynthetase syndrome, highlighting the critical importance of comprehensive myositis autoantibody testing in this population. As in other types of ILD, male sex may portend a worse prognosis in IPAF. The routine engagement of rheumatologists in the multidisciplinary evaluation of ILD will help ensure the accurate classification of these patients and help clarify prognostic factors.
Assuntos
Doenças Autoimunes , Doenças do Tecido Conjuntivo , Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Miosite , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/diagnóstico , Humanos , Fibrose Pulmonar Idiopática/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Masculino , Miosite/complicações , Miosite/diagnóstico , PrognósticoRESUMO
OBJECTIVES: Telomere shortening is a well-established marker of biological aging. Whether telomere erosion coincides with age-related increases in antinuclear antibody (ANA) seropositivity remains unknown. Our study aimed to determine the association between ANA seropositivity and shortened telomeres among 1999-2002 National Health and Nutrition Examination Survey (NHANES) subjects. METHODS: We performed a cross-sectional analysis of 2,188 NHANES study participants with available ANA and telomere length data. ANA testing was performed using indirect immunofluorescence. Telomere lengths were measured via quantitative polymerase chain reaction methods. Applying appropriate sample weighting techniques, we used univariate and multivariate logistic regression methods to assess the association between shortened telomeres (i.e. lowest decile of the cohort) and ANA seropositivity. RESULTS: ANAs were positive in 322 out of 2,188 (14.7%, 95% CI 13.3-16.3%) individuals. Subjects with shortened telomeres were more likely to be older (p<0.001), male (p=0.005), and have a cancer history (p<0.001). A higher proportion of non-Hispanic white participants (61.6% vs. 49.3%) and a lower proportion of non-Hispanic black participants (7.8% vs. 17.9%) had shortened telomeres (p<0.001). Shortened telomeres were not independently associated with ANA seropositivity (OR 1.48, 95% CI 0.87-2.52, p=0.14). However, female sex (OR 1.91, 95% CI 1.23-2.96, p=0.006), age ≥80 years (OR 2.06, 95% CI 1.08-3.92, p=0.03), and African American race (OR 1.58, 95% CI 1.00-2.51, p=0.05) were independent risk factors for ANA seropositivity. Neither sex nor race modified the relationship between ANA seropositivity and telomere length. CONCLUSIONS: Telomere erosion does not appear to be responsible for age-related increases in the prevalence of ANA seropositivity.
Assuntos
Anticorpos Antinucleares , Telômero , Envelhecimento , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos Nutricionais , Telômero/genéticaRESUMO
OBJECTIVES: To study the efficacy in terms of muscle strength, and corticosteroid tapering as well as the prevalence of adverse effects in patients with the antisynthetase syndrome (ASyS) treated with azathioprine (AZA) compared to those treated with methotrexate (MTX). METHODS: We compared the clinical outcomes in ASyS patients treated with AZA versus MTX including change in corticosteroid dose, strength, and creatine kinase (CK) as well as the prevalence of adverse effects. RESULTS: Among 169 patients with ASyS, 102 were treated at some point exclusively with either AZA or MTX (± corticosteroids). There were no significant differences in the rate of muscle strength recovery, CK decrease or corticosteroid tapering between those ASyS patients treated with MTX versus AZA. The prevalence of adverse events in patients treated with AZA and MTX was similar (29% vs. 25%, p>0.05); elevated liver enzymes (17% AZA vs. 12% MTX) and gastrointestinal involvement (10% AZA vs. 8% MTX) were the most common adverse events. While no patients treated with AZA developed lung complications, two of the patients treated with MTX experienced reversible pneumonitis with MTX cessation. CONCLUSIONS: AZA and MTX showed similar efficacy and adverse events in patients with ASyS. Pneumonitis is a rare but important event in patients receiving MTX.
Assuntos
Azatioprina , Metotrexato , Miosite/tratamento farmacológico , Corticosteroides , Azatioprina/efeitos adversos , Azatioprina/uso terapêutico , Creatina Quinase/sangue , Humanos , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Força Muscular/efeitos dos fármacos , Força Muscular/fisiologiaRESUMO
PURPOSE OF REVIEW: To provide an overview of recently published articles covering interstitial lung disease associated with rheumatoid arthritis (RA-ILD). RECENT FINDINGS: Over the past year, many studies replicated previous findings in more diverse and occasionally larger populations internationally. Specifically, the association among cigarette smoking, high rheumatoid factor titer, elevated anticitrullinated protein antibody (ACPA) levels, and RA-ILD was strengthened. Clinical characteristics, autoantibodies, and biomarkers to aid in RA-ILD development, progression, and mortality prediction were explored. Finally, direct and indirect treatment effects were highlighted. SUMMARY: The ability to identify risk factors for preclinical RA-ILD has been enhanced, but the proper management strategy for these patients is yet to be defined. ACPAs and cigarette smoking are highly associated with RA-ILD, but the mechanistic relationship between lung injury and autoantibody generation remains unknown. There is conflicting evidence regarding the significance of a usual interstitial pneumonia (UIP) versus non-UIP pattern on high-resolution computed tomography. The use of biologic agents in patients with rheumatoid arthritis does not appear to increase the risk of incident ILD or RA-ILD exacerbation. Randomized prospective studies of specific therapy for RA-ILD are still lacking.
Assuntos
Artrite Reumatoide , Gerenciamento Clínico , Doenças Pulmonares Intersticiais , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/terapia , Biomarcadores/metabolismo , Progressão da Doença , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/terapia , Tomografia Computadorizada por Raios X/métodosRESUMO
Objective: The aim was to study the prevalence, rate of appearance and severity of clinical features in patients with different anti-synthetase syndrome (ASyS) autoantibodies. Methods: All Johns Hopkins Myositis Longitudinal Cohort subjects positive for any ASyS autoantibodies were included. Clinical information, including symptoms, signs, strength, creatine kinase concentrations and pulmonary function tests, were prospectively collected. The standardized mortality and cancer rates and the rate of appearance and intensity of the different organ manifestations were assessed using univariate and multivariate analysis and compared between ASyS autoantibodies. Results: One hundred and twenty-four (73.4%) patients were positive for anti-Jo1, 23 (13.6%) for anti-PL12, 16 for anti-PL7 (9.5%) and 3 (1.8%) for anti-EJ or anti-OJ, respectively. The mean length of follow-up was 4.1 years. Anti-PL12 was more frequent in black subjects. Anti-PL12 and anti-PL7 were associated with more prevalent and severe lung involvement, often without muscle involvement. Anti-Jo1 displayed more severe muscle involvement compared with anti-PL12 patients. Concurrent anti-Ro52 was more prevalent in anti-Jo1 patients and was associated with earlier development of mechanic's hands, DM-specific skin findings and arthritis. Independent of ASyS antibody status, black patients demonstrated more severe lung involvement than white patients. There was no significant increase in mortality or cancer risk in ASyS patients compared with the general US population. Conclusion: Different ASyS autoantibodies are associated with phenotypically distinct subgroups within the ASyS spectrum. Anti-PL7 and anti-PL12 are characterized by more severe lung involvement, whereas anti-Jo1 is associated with more severe muscle involvement. Black race is a major prognostic factor associated with lung disease severity.
Assuntos
Autoanticorpos/metabolismo , Doenças Pulmonares Intersticiais/imunologia , Miosite/imunologia , Negro ou Afro-Americano/etnologia , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Doenças Pulmonares Intersticiais/etnologia , Masculino , Pessoa de Meia-Idade , Doenças Musculares/imunologiaRESUMO
PURPOSE: Among patients with autoimmune myositis, associated interstitial lung disease (MA-ILD) is a known contributor of excess morbidity and mortality. Recent data on survival in idiopathic inflammatory myopathies originate primarily in Asia and Europe and vary widely. We sought to examine mortality in a large U.S. myositis cohort focusing in particular on the impact of associated ILD. METHODS: A cross-sectional analysis of participants from the Johns Hopkins Myositis Center with autoimmune myositis (polymyositis [PM], dermatomyositis [DM], or clinically amyopathic dermatomyositis [CADM]) was conducted. The primary outcome assessed was all-cause mortality. Cumulative mortality rates were estimated using the Kaplan-Meier test; the Cox proportional hazards model was used to compare group differences in survival. RESULTS: Eight hundred and thirty-one participants were included with a median follow-up time of 4.5 years. Four hundred thirty-eight (53 %) had PM, 362 (43 %) had DM, and 31 (4 %) had CADM. Ninety-four (11 %) participants had clinically evident ILD. Overall, 51 participants died (6 %). In those without ILD, the survival rates at 1, 5, and 10 years were 99, 95, and 90 %, respectively. In those with ILD, the survival rates at 1, 5, and 10 years were 97, 91, and 81 %, respectively. The risk of death was statistically significantly higher among participants with ILD compared to those without ILD (HR 2.13. 95 % CI 1.06-4.25; p = 0.03). CONCLUSIONS: We analyzed one of the largest known cohorts of patients with autoimmune myositis and found significantly higher mortality rates among those with clinically evident ILD compared to those without clinically evident ILD. Our results suggest that ILD remains an important and significant source of mortality in patients with inflammatory myopathies and as such should be screened for and treated aggressively.
Assuntos
Doenças Autoimunes/mortalidade , Dermatomiosite/mortalidade , Doenças Pulmonares Intersticiais/mortalidade , Adulto , Idoso , Doenças Autoimunes/complicações , Estudos Transversais , Dermatomiosite/complicações , Feminino , Humanos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Capacidade de Difusão Pulmonar , Estudos Retrospectivos , Taxa de Sobrevida , Capacidade Pulmonar Total , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.
Assuntos
Doenças Autoimunes , Doenças Pulmonares Intersticiais , Doenças Reumáticas , Reumatologia , Humanos , Doenças Pulmonares Intersticiais/terapia , Doenças Reumáticas/complicações , Doenças Reumáticas/tratamento farmacológico , Doenças Autoimunes/complicações , Doenças Autoimunes/terapia , Reumatologia/normas , Glucocorticoides/uso terapêutico , Medicina Baseada em Evidências/normasRESUMO
OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.
Assuntos
Doenças Autoimunes , Doenças Pulmonares Intersticiais , Doenças Reumáticas , Reumatologia , Doenças Pulmonares Intersticiais/diagnóstico , Humanos , Doenças Reumáticas/complicações , Doenças Reumáticas/diagnóstico , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/complicações , Reumatologia/normas , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Testes de Função Respiratória , Tomografia Computadorizada por Raios X , Artrite Reumatoide/complicações , Sociedades Médicas , Estados Unidos , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Doença Mista do Tecido Conjuntivo/complicações , Doença Mista do Tecido Conjuntivo/diagnóstico , Miosite/diagnóstico , Miosite/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/complicações , Teste de CaminhadaRESUMO
OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.
Assuntos
Doenças Autoimunes , Doenças Pulmonares Intersticiais , Doenças Reumáticas , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Reumáticas/complicações , Doenças Reumáticas/diagnóstico , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Reumatologia/normas , Programas de Rastreamento/normas , Programas de Rastreamento/métodosRESUMO
OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.
Assuntos
Doenças Autoimunes , Glucocorticoides , Doenças Pulmonares Intersticiais , Doenças Reumáticas , Reumatologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Humanos , Doenças Reumáticas/complicações , Doenças Reumáticas/tratamento farmacológico , Glucocorticoides/uso terapêutico , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Reumatologia/normas , Escleroderma Sistêmico/complicações , Estados Unidos , Progressão da Doença , Sociedades MédicasRESUMO
BACKGROUND: Diagnosis of diffuse parenchymal lung diseases (DPLD) on high resolution CT (HRCT) is difficult for non-expert radiologists due to varied presentation for any single disease and overlap in presentation between diseases. RATIONALE AND OBJECTIVES: To evaluate whether a pattern-based training algorithm can improve the ability of non-experts to diagnosis of DPLD. MATERIALS AND METHODS: Five experts (cardiothoracic-trained radiologists), and 25 non-experts (non-cardiothoracic-trained radiologists, radiology residents, and pulmonologists) were each assigned a semi-random subset of cases from a compiled database of DPLD HRCTs. Each reader was asked to create a top three differential for each case. The non-experts were then given a pattern-based training algorithm for identifying DPLDs. Following training, the non-experts were again asked to create a top three differential for each case that they had previously evaluated. Accuracy between groups was compared using Chi-Square analysis. RESULTS: A total of 400 and 1450 studies were read by experts and non-experts, respectively. Experts correctly placed the diagnosis as the first item on the differential versus having the correct diagnosis as one of their top three diagnoses at an overall rate of 48 and 64.3%, respectively. Pre-training, non-experts achieved a correct diagnosis/top three of 32.5 and 49.7%, respectively. Post-training, non-experts demonstrated a correct diagnosis/top three of 41.2 and 65%, a statistically significant increase (p < 0.0001). In addition, post training, there was no difference between non-experts and experts in placing the correct diagnosis within their top three differential. CONCLUSION: The diagnosis of DPLDs by HRCT imaging alone is relatively poor. However, use of a pattern-based teaching algorithm can improve non-expert interpretation and enable non-experts to include the correct diagnosis within their differential diagnoses at a rate comparable to expert cardiothoracic trained radiologists.
Assuntos
Doenças Pulmonares Intersticiais , Algoritmos , Diagnóstico Diferencial , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Radiologistas , Tomografia Computadorizada por Raios X/métodosRESUMO
Rationale: Prior studies investigating associations of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) seropositivity with risk for rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) have mostly used cross-sectional or case-control designs.Objectives: To determine whether combined autoantibody seropositivity and higher individual autoantibody concentrations were associated with increased risk for RA-ILD in a prospective RA cohort.Methods: Within the Veterans Affairs Rheumatoid Arthritis prospective registry, we performed a cross-sectional study of prevalent ILD and a retrospective cohort study of incident ILD (diagnosed after at least 12 mo of longitudinal follow-up). We used logistic and Cox regression methods to determine whether combined RF/ACPA seropositivity and higher autoantibody concentrations were independently associated with greater risk for prevalent and incident ILD, respectively.Results: Among 2,328 participants (median age 64 yr, 89.3% male), 100 (4.3%) subjects had prevalent ILD at enrollment. During 14,281 patient-years of follow-up, 83 (3.7%) of the remaining 2,228 were subsequently diagnosed with incident ILD (5.8 cases per 1,000 person-years). Patients with combined RF/ACPA seropositivity had a higher probability of prevalent ILD compared with seronegative subjects (odds ratio [OR], 2.90; 95% confidence interval [CI], 1.24-6.78). RF titers demonstrated a monotonic association with prevalent ILD (OR, 2.69; 95% CI, 1.11-6.51 for low-positive [15-45 IU/ml] titers; OR, 3.40; 95% CI, 1.61-7.18 for high-positive [>45 IU/ml] titers; P for trend 0.01). Patients with high-positive (>15 U/ml) ACPA titers were also at higher risk for prevalent ILD (OR, 1.91; 95% CI, 1.04-3.49) compared with ACPA-negative subjects. Combined RF/ACPA seropositivity was not associated with increased risk for incident ILD, nor were high- or low-positive RF or ACPA titers. In a piecewise linear spline model, however, RF titers greater than 90 IU/ml independently correlated with increased risk for incident ILD (hazard ratio, 1.68, 95% CI, 1.02-2.77).Conclusions: Combined RF/ACPA seropositivity and individual autoantibody concentrations were strongly associated with prevalent but not incident RA-ILD. Only patients with RF concentrations >90 IU/ml were observed to be at higher risk of incident RA-ILD.
Assuntos
Artrite Reumatoide , Doenças Pulmonares Intersticiais , Veteranos , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Doenças Pulmonares Intersticiais/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
PURPOSE: Myositis-associated interstitial lung disease (MA-ILD) is associated with increased mortality, but no prognostic model exists in this population. The ILD-GAP index was developed to predict mortality risk across all subtypes of chronic ILD. The purpose of this study was to validate the ILD-GAP risk prediction model in patients with MA-ILD. PROCEDURES: We completed a retrospective cross-sectional study of patients enrolled in the Johns Hopkins Myositis Center database between 2006 and 2017. Cumulative mortality rates were estimated using the Kaplan-Meier test. Model calibration was determined by using standardized mortality ratios of observed versus expected deaths. MAIN FINDINGS: 179 participants with MA-ILD were included. The mean baseline percent predicted forced vital capacity was 65.2⯱â¯20.6%, forced expiratory volume in the first second 65.4⯱â¯20.4%, and carbon monoxide diffusing capacity 61.6⯱â¯20.0%. Thirty-two participants died (17.9%). The ILD-GAP model had poor discriminative performance and calibration. CONCLUSIONS: The ILD-GAP risk prediction model is a poor predictor of mortality among individuals with MA-ILD. The identification of a better predictive model for MA-ILD is needed to help guide care in this patient population.
Assuntos
Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/fisiopatologia , Miosite/complicações , Miosite/mortalidade , Idoso , Calibragem/normas , Regras de Decisão Clínica , Estudos Transversais , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/epidemiologia , Masculino , Pessoa de Meia-Idade , Miosite/epidemiologia , Miosite/patologia , Prevalência , Prognóstico , Testes de Função Respiratória/métodos , Testes de Função Respiratória/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco , Capacidade Vital/fisiologiaRESUMO
OBJECTIVE: To define the clinical phenotype of patients with myositis with anti-U1-ribonucleoprotein (RNP) autoantibodies. METHODS: In this longitudinal cohort study, the prevalence and severity of clinical features at disease onset and during follow-up in patients with anti-U1-RNP-positive myositis were compared to those with dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), and the antisynthetase syndrome (AS). RESULTS: Twenty anti-U1-RNP-positive patients, 178 patients with DM, 135 patients with IMNM, and 132 patients with AS were included. Anti-U1-RNP-positive patients were younger (â¼37 years) and more likely to be black (60%) than patients with AS, DM, or IMNM. Muscle weakness was a presenting feature in 15% of anti-U1-RNP-positive patients; 80% eventually developed weakness. Four of 7 anti-U1-RNP-positive patients had necrotizing muscle biopsies. Arthritis occurred in 60% of anti-U1-RNP-positive patients; this was increased compared to DM (18%) or IMNM (6%) (all p < 0.01). DM-specific skin features developed in 60% of anti-U1-RNP-positive patients. Interstitial lung disease (ILD) occurred in 45% of anti-U1-RNP-positive patients; fewer patients with DM (13%) and IMNM (6%) and more patients with AS (80%) developed ILD (all p < 0.01). Glomerulonephritis and pericarditis occurred in 25% and 40% of anti-U1-RNP-positive patients, respectively, but rarely in the other groups; these features occurred only in those with coexisting anti-Ro52 autoantibodies. No anti-U1-RNP patient had cancer-associated myositis or died during the study period. CONCLUSIONS: Patients with anti-U1-RNP myositis typically present with proximal weakness and necrotizing muscle biopsies. Arthritis, dermatitis, and ILD are the most common extramuscular clinical features. Pericarditis and glomerulonephritis are uniquely found in patients with anti-U1-RNP-positive myositis.
Assuntos
Artrite/fisiopatologia , Doenças Autoimunes/fisiopatologia , Glomerulonefrite/fisiopatologia , Debilidade Muscular/fisiopatologia , Miosite/fisiopatologia , Pericardite/fisiopatologia , Adulto , Negro ou Afro-Americano , Idade de Início , Idoso , Artrite/etiologia , Autoanticorpos/imunologia , Doenças Autoimunes/complicações , Doenças Autoimunes/etnologia , Estudos de Casos e Controles , Estudos de Coortes , Dermatomiosite/etnologia , Dermatomiosite/fisiopatologia , Feminino , Glomerulonefrite/etiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Músculo Esquelético/patologia , Miosite/complicações , Miosite/etnologia , Miosite/imunologia , Necrose , Pericardite/etiologia , Ribonucleoproteína Nuclear Pequena U1/imunologia , População Branca , Adulto JovemRESUMO
BACKGROUND: The efficacy of azathioprine (AZA) and mycophenolate mofetil (MMF) for interstitial lung disease (ILD) has been described, but mainly in connective tissue disease-associated ILD. The objective of this study was to evaluate the effect of AZA and MMF on lung function and prednisone dose in myositis-related ILD (M-ILD). METHODS: In this retrospective study, patients with M-ILD seen at Johns Hopkins and treated with AZA or MMF and no other steroid-sparing agents were included. Linear mixed-effects models adjusted for sex, age, antisynthetase antibody, and smoking status were used to compare the change in FVC % predicted, diffusing capacity of the lungs for carbon monoxide (Dlco) % predicted, and prednisone dose. RESULTS: Sixty-six patients with M-ILD were treated with AZA and 44 with MMF. At treatment initiation, mean FVC % predicted and Dlco % predicted were significantly lower in the AZA group than in the MMF group. In both groups, FVC % predicted improved and the prednisone dose was reduced over 2 to 5 years; however, for Dlco % predicted, only the AZA group improved. The adjusted model showed no significant difference in posttreatment FVC % predicted or Dlco % predicted between groups (mean difference of 1.9 and -8.2, respectively), but a 6.6-mg lower dose of prednisone at 36 months in the AZA group. Adverse events were more frequent with AZA than MMF (33.3% vs 13.6%; P = .04). CONCLUSIONS: In M-ILD, AZA treatment was associated with improved FVC % predicted and Dlco % predicted, and lower prednisone dose. Patients treated with MMF had improved FVC % predicted and lower prednisone dose. After 36 months, patients treated with AZA received a lower prednisone dose than those treated with MMF.
Assuntos
Azatioprina/uso terapêutico , Volume Expiratório Forçado/fisiologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Miosite/complicações , Inibidores Enzimáticos/uso terapêutico , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Miosite/tratamento farmacológico , Prednisona/uso terapêutico , Testes de Função Respiratória , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
OBJECTIVE: To define the clinical phenotype of dermatomyositis (DM) with anti-Mi2 autoantibodies. METHODS: In this longitudinal cohort study, the prevalence and severity of clinical features at disease onset and during follow-up in patients with anti-Mi2-positive DM were compared to patients with anti-Mi2-negative DM, antisynthetase syndrome (AS), and immune-mediated necrotizing myopathy (IMNM). Longitudinal anti-Mi2 autoantibody titers were assessed. RESULTS: A total of 58 patients with anti-Mi2-positive DM, 143 patients with anti-Mi2-negative DM, 162 patients with AS, and 170 patients with IMNM were included. Among patients with anti-Mi2-positive DM, muscle weakness was present in 60% at disease onset and occurred in 98% during longitudinal follow-up; fewer patients with anti-Mi2-negative DM developed weakness (85%; p = 0.008). Patients with anti-Mi2-positive DM were weaker and had higher creatine kinase (CK) levels than patients with anti-Mi2-negative DM or patients with AS. Muscle biopsies from patients with anti-Mi2-positive DM had prominent necrosis. Anti-Mi2 autoantibody levels correlated with CK levels and strength (p < 0.001). With treatment, most patients with anti-Mi2-positive DM had improved strength and CK levels; among 10 with multiple serum samples collected over 4 or more years, anti-Mi2 autoantibody titers declined in all and normalized in 3, 2 of whom stopped immunosuppressant treatment and never relapsed. Patients with anti-Mi2-positive DM had less calcinosis (9% vs 28%; p = 0.003), interstitial lung disease (5% vs 16%; p = 0.04), and fever (7% vs 21%; p = 0.02) than did patients with anti-Mi2-negative DM. CONCLUSIONS: Patients with anti-Mi2-positive DM have more severe muscle disease than patients with anti-Mi2-negative DM or patients with AS. Anti-Mi2 autoantibody levels correlate with disease severity and may normalize in patients who enter remission.
Assuntos
Autoanticorpos/imunologia , Calcinose/epidemiologia , Dermatomiosite/imunologia , Febre/epidemiologia , Doenças Pulmonares Intersticiais/epidemiologia , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/imunologia , Debilidade Muscular/epidemiologia , Adulto , Idoso , Calcinose/fisiopatologia , Estudos de Casos e Controles , Estudos de Coortes , Creatina Quinase/sangue , Dermatomiosite/sangue , Dermatomiosite/epidemiologia , Dermatomiosite/fisiopatologia , Feminino , Humanos , Estudos Longitudinais , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/fisiopatologia , Miosite/imunologia , Miosite/fisiopatologia , Necrose , Fenótipo , Prevalência , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To define the clinical features of myositis patients with anti-PM/Scl-75 and/or anti-PM/Scl-100 autoantibodies at disease onset and during the course of disease and compare them to patients with other forms of myositis. METHODS: In this longitudinal cohort study, the prevalence and severity of clinical features at disease onset and during follow-up were compared between anti-PM/Scl-positive patients and those with the antisynthetase syndrome (AS), dermatomyositis (DM), and immune-mediated necrotizing myopathy (IMNM). RESULTS: Forty-one anti-PM/Scl-positive, 132 AS, 178 DM, and 135 IMNM patients were included. Although muscle weakness was a presenting feature in just 37% of anti-PM/Scl-positive patients, 93% eventually developed weakness. Unlike the other groups, anti-PM-Scl-positive patients had more severe weakness in arm abductors than hip flexors. Interstitial lung disease was a presenting feature in just 10% of anti-PM/Scl-positive patients, but occurred in 61% during follow-up; fewer patients with DM (13%, p < 0.001) and IMNM (6%, p < 0.001) and more patients with AS (80%, p < 0.05) developed interstitial lung disease during the course of disease. Mechanic's hands (80%), Raynaud syndrome (78%), sclerodactyly (66%), telangiectasias (66%), esophageal reflux disease (61%), subcutaneous edema (46%), puffy hands (39%), and calcinosis (39%) occurred more frequently in anti-PM/Scl-positive patients than in the other groups. Although 30% of anti-PM/Scl-positive patients met criteria for systemic sclerosis, less than 5% had renal crisis or finger ulcerations. No differences were found between patients with only anti-PM/Scl-100 or only anti-PM/Scl-75 autoantibodies. CONCLUSIONS: Unlike patients with DM, AS, or IMNM, anti-PM/Scl-positive patients have weaker arm abductors than hip flexors. Anti-PM/Scl-positive patients also have the most extensive extramuscular features.
Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/sangue , Dermatomiosite/sangue , Complexo Multienzimático de Ribonucleases do Exossomo/imunologia , Músculo Esquelético/patologia , Miosite/sangue , Adulto , Idoso , Doenças Autoimunes/diagnóstico por imagem , Doenças Autoimunes/terapia , Estudos de Coortes , Creatina Quinase/sangue , Dermatomiosite/diagnóstico por imagem , Dermatomiosite/terapia , Eletromiografia , Feminino , Humanos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiopatologia , Miosite/diagnóstico por imagem , Miosite/terapia , Análise de Regressão , Testes de Função RespiratóriaRESUMO
OBJECTIVE: Dermatomyositis (DM) patients typically present with proximal weakness and autoantibodies that are associated with distinct clinical phenotypes. We observed that DM patients with autoantibodies recognizing the nuclear matrix protein NXP-2 often presented with especially severe weakness. The aim of this study was to characterize the clinical features associated with anti-NXP-2 autoantibodies. METHODS: There were 235 DM patients who underwent testing for anti-NXP-2 autoantibodies. Patient characteristics, including muscle strength, were compared between those with and without these autoantibodies. The number of cancer cases observed in anti-NXP-2-positive subjects was compared with the number expected in the general population. RESULTS: Of the DM patients, 56 (23.8%) were anti-NXP-2-positive. There was no significant difference in the prevalence of proximal extremity weakness in patients with and without anti-NXP-2. In contrast, anti-NXP-2-positive patients had more prevalent weakness in the distal arms (35% versus 20%; P = 0.02), distal legs (25% versus 8%; P < 0.001), and neck (48% versus 23%; P < 0.001). Anti-NXP-2-positive subjects were also more likely to have dysphagia (62% versus 35%; P < 0.001), myalgia (46% versus 25%; P = 0.002), calcinosis (30% versus 17%; P = 0.02), and subcutaneous edema (36% versus 19%; P = 0.01) than anti-NXP-2-negative patients. Five anti-NXP-2-positive subjects (9%) had cancer-associated myositis, representing a 3.68-fold increased risk (95% confidence interval 1.2-8.6) compared to the expected prevalence in the general population. CONCLUSION: In DM, anti-NXP-2 autoantibodies are associated with subcutaneous edema, calcinosis, and a muscle phenotype characterized by myalgia, proximal and distal weakness, and dysphagia. As anti-NXP-2-positive patients have an increased risk of cancer, we suggest that they undergo comprehensive cancer screening.