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OBJECTIVES: Excessive and inappropriate production of pro-inflammatory cytokines plays a key role in Still's disease. Janus kinase inhibitor (JAKi) agents mainly block pro-inflammatory cytokine pathways, notably IL-6 and IFN. The objective was to assess the efficacy and safety of JAKi agents in difficult-to-treat systemic JIA or adult-onset Still's disease (AOSD). METHODS: This retrospective study was based on a national survey conducted in the departments of rheumatology, paediatric rheumatology and internal medicine of French hospitals regarding systemic JIA and AOSD patients who received JAKi agents. The data were collected with a standardized questionnaire and analysed at different times (treatment initiation, months 1, 3 and 6 and the end of follow-up). RESULTS: Nine patients (seven adults) were included. All patients showed inadequate response to CS or conventional synthetic or biologic DMARDs. Baricitinib was used in five patients, ruxolitinib in two, tofacitinib in two and upadacitinib in one. A JAKi was used combined with CS in all but two patients. A JAKi was associated with anakinra and CS in one patient, and with MTX, anakinra and CS in another. The median (range) follow-up was 16 (1-33) months. Two cases out of nine showed complete remission, 3/9 partial response and 4/9 treatment failure. At the last visit, CS could be decreased but not stopped. Tolerance of the JAKi was acceptable (no severe adverse events). CONCLUSION: JAKi agents may be a therapeutic option for some patients with difficult-to-treat Still's disease, especially those with partial response to medium- or high-dose CS or biologics.
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Antirreumáticos , Artrite Juvenil , Inibidores de Janus Quinases , Doença de Still de Início Tardio , Adulto , Criança , Humanos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Doença de Still de Início Tardio/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Antirreumáticos/uso terapêutico , CitocinasAssuntos
Antirreumáticos , Artrite Psoriásica , Artrite Reumatoide , Espondiloartrite Axial , Espondilartrite , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Humanos , Dor/tratamento farmacológico , Estudos Prospectivos , Espondilartrite/complicações , Espondilartrite/diagnóstico , Espondilartrite/epidemiologiaRESUMO
OBJECTIVES: Systemic-onset JIA (SJIA) and adult-onset Still's disease (AOSD) are the same sporadic systemic auto-inflammatory disease. SpA is a group of inflammatory non-autoimmune disorders. We report the observations of eight patients with SJIA/AOSD who also presented features of SpA during their disease evolution and estimate the prevalence of SpA in SJIA/AOSD. METHODS: This was a retrospective national survey of departments of paediatric and adult rheumatology and internal medicine. To be included, SJIA patients had to fulfil the ILAR criteria, AOSD patients the Yamaguchi or Fautrel criteria, and all patients the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axial or peripheral SpA, ESSG criteria for SpA or Classification Criteria for Psoriatic Arthritis (CASPAR) criteria for PsA. The data were collected with a standardized form. RESULTS: Eight patients (five adults) were identified in one paediatric and two adult departments. In all but one patient, SpA manifestations occurred several years after SJIA/AOSD onset [mean (s.d.) delay 6.2 (3.8) years]. Two patients had peripheral and three axial SpA, and four later exhibited PsA and one SAPHO syndrome. The prevalence of SpA in an adult cohort of 76 patients with AOSD was 6.58% (95% CI 2.17, 14.69), greater than the prevalence of SpA in the French general population (0.3%; 95% CI 0.17, 0.46). The prevalence of SpA in an SJIA cohort of 30 patients was 10% (95% CI 2.11, 26.53), more than that reported in the general population of industrialized countries, estimated at 0.016-0.15%. CONCLUSION: While the temporal disassociation between SpA and AOSD in most cases might suggest a coincidental finding, our work raises the possibility of an SpA/AOSD spectrum overlap that needs further study.
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Artrite Juvenil , Artrite Psoriásica , Doença de Still de Início Tardio , Adulto , Artrite Juvenil/epidemiologia , Artrite Juvenil/genética , Artrite Psoriásica/epidemiologia , Criança , Humanos , Fenótipo , Estudos Retrospectivos , Doença de Still de Início Tardio/epidemiologiaRESUMO
BACKGROUND: Barriers and facilitators to physical activity in inflammatory arthritis can be assessed through the Inflammatory arthritis FAcilitators and Barriers (IFAB) questionnaire. The objective was to measure the correlation between IFAB and self-reported physical activity levels. METHODS: This was an international, multicentric, cross-sectional study in 2019-20. Consecutive spondyloarthritis (axSpA), rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients completed the 10-item IFAB, which ranges from - 70 to 70 with lower scores indicating more barriers. Physical activity was measured by the IPAQ-S questionnaire, steps per day collected by smartphone, and psychological readiness to change by stages of behaviour change. Spearman correlations and multivariable linear regression were calculated. RESULTS: Of 245 patients included, 150 were analysed: 69 (46%) axSpA, 63 (42%) RA, 18 (12%) PsA. Mean age was 48.6 years (standard deviation, SD 17.1), mean disease duration 11.7 (10.1) years and 60% were women. Barriers to physical activity were moderate: mean IFAB, 6 (SD 19.2); 39 (26%) patients scored less than - 5, corresponding to significant barriers. The mean physical activity was 2837 (SD 2668, median 1784) MET-minutes per week. The IPAQ-S questionnaire was correlated with the IFAB (rho 0.28, p < 0.001), as well as the stage of behaviour change (rho 0.35, p < 0.001) though not with steps per day. Multivariable analyses were confirmatory. CONCLUSION: Perceived barriers and facilitators to physical activity were correlated with physical activity, indicating that targeting patients with high barriers and low facilitators to physical activity could be an effective option to improve physical activity levels. TRIAL REGISTRATION: ClinicalTrial NCT04426747 . Registered 11 June 2020 - Retrospectively registered.
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Artrite Psoriásica , Artrite Reumatoide , Espondilartrite , Artrite Reumatoide/diagnóstico , Estudos Transversais , Exercício Físico , Feminino , Humanos , Pessoa de Meia-Idade , Espondilartrite/diagnósticoRESUMO
Adult-onset Still's disease (AOSD) is a non-familial, polygenic systemic autoinflammatory disorder. It is traditionally characterized by four cardinal manifestations-spiking fever, an evanescent salmon-pink maculopapular rash, arthralgia or arthritis and a white-blood-cell count (WBC) ≥ 10,000/mm3, mainly neutrophilic polymorphonuclear cells (PMNs)-but many other manifestations and complications can be associated, making clinical expression very heterogeneous and diagnosis sometimes difficult. The AOSD course can be diverse and is currently impossible to predict. Several clinical phenotypes have been described, either on the basis of the evolution of symptoms over time (monocyclic, polycyclic and chronic evolution) or according to dominant clinical evolution (systemic and arthritis subtypes). However, these patterns are mainly based on case series and not on robust epidemiological studies. Furthermore, they have mainly been established a long time ago, before the era of the biological treatments. Thus, based on our personal experience and on recent advances in the understanding of disease pathogenesis, it appears interesting to reshuffle AOSD phenotypes, emphasizing the continuum between AOSD profiles and other systemic autoinflammatory disorders, eventually proposing a research agenda.
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OBJECTIVES: Remission (REM) or low disease activity (LDA) is the treatment target in psoriatic arthritis (PsA). The objective of this study was to assess the reporting and prevalence of REM/LDA in published studies of PsA. METHODS: This was a systematic literature review of all clinical papers published in PubMed, EMBASE or Cochrane database in English between 2012 and 2019 in the field of PsA. Data were collected regarding reporting of REM/LDA by very low disease activity/minimal disease activity (VLDA/MDA), Disease Activity index for Psoriatic Arthritis (DAPSA), or Disease Activity Score 28 joints (DAS28). The pooled rates of REM and LDA by each definition were calculated by random effect meta-analysis. RESULTS: In all, 258 publications (corresponding to 114 651 patients), of which 81 (31%) were randomized controlled trials, were analysed: patients' mean age was 49.4 ( 4.4) years; with a mean disease duration of 8.5 ( 3.8) years. REM/LDA was reported in 91/258 (35.3%) publications. VLDA/MDA was used in 61/91 (67.0%) studies, DAPSA in 27/91 (29.6%) and DAS28 in 28/91 (30.7%), with 40/91 (43.9%) papers reporting several of these definitions. The pooled prevalence (lower-upper limits) of REM was 13.1% (10.9-15.4), 23.1% (16.8-30.1) and 42.1% (33.9-50.4) using VLDA, DAPSA-REM and DAS28, respectively. For LDA the pooled prevalence was 36.3% (32.3-40.5), 52.8% (41.8-63.6) and 60.4% (52.5-68.0) using MDA, DAPSA-LDA and DAS28, respectively. CONCLUSION: REM/LDA status was reported in only1/3 of recent studies on PsA, with important variations in the frequency of these outcomes according to the definition used: 13.1-42.1% for REM, and 36.3-60.4% for LDA. This highlights the need for consensus.
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Antirreumáticos/uso terapêutico , Artrite Psoriásica/diagnóstico , Indução de Remissão , Artrite Psoriásica/tratamento farmacológico , Humanos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
In 2017 in France, we treated a patient with knee septic arthritis caused by Erwinia billingiae after trauma involving a palm tree. This rare pathogen could only be identified through 16S rRNA gene sequencing. For bacterial infections after injuries with plants, 16S rRNA gene sequencing might be required for species identification.
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Artrite Infecciosa/diagnóstico , Artrite Infecciosa/microbiologia , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Erwinia , Idoso , Antibacterianos/uso terapêutico , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/história , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/história , Erwinia/classificação , Erwinia/genética , França , História do Século XXI , Humanos , Masculino , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Resultado do TratamentoRESUMO
OBJECTIVE: Flares in rheumatoid arthritis (RA) and axial spondyloarthritis (SpA) may influence physical activity. The aim of this study was to assess longitudinally the association between patient-reported flares and activity-tracker-provided steps per minute, using machine learning. METHODS: This prospective observational study (ActConnect) included patients with definite RA or axial SpA. For a 3-month time period, physical activity was assessed continuously by number of steps/minute, using a consumer grade activity tracker, and flares were self-assessed weekly. Machine-learning techniques were applied to the data set. After intrapatient normalization of the physical activity data, multiclass Bayesian methods were used to calculate sensitivities, specificities, and predictive values of the machine-generated models of physical activity in order to predict patient-reported flares. RESULTS: Overall, 155 patients (1,339 weekly flare assessments and 224,952 hours of physical activity assessments) were analyzed. The mean ± SD age for patients with RA (n = 82) was 48.9 ± 12.6 years and was 41.2 ± 10.3 years for those with axial SpA (n = 73). The mean ± SD disease duration was 10.5 ± 8.8 years for patients with RA and 10.8 ± 9.1 years for those with axial SpA. Fourteen patients with RA (17.1%) and 41 patients with axial SpA (56.2%) were male. Disease was well-controlled (Disease Activity Score in 28 joints mean ± SD 2.2 ± 1.2; Bath Ankylosing Spondylitis Disease Activity Index score mean ± SD 3.1 ± 2.0), but flares were frequent (22.7% of all weekly assessments). The model generated by machine learning performed well against patient-reported flares (mean sensitivity 96% [95% confidence interval (95% CI) 94-97%], mean specificity 97% [95% CI 96-97%], mean positive predictive value 91% [95% CI 88-96%], and negative predictive value 99% [95% CI 98-100%]). Sensitivity analyses were confirmatory. CONCLUSION: Although these pilot findings will have to be confirmed, the correct detection of flares by machine-learning processing of activity tracker data provides a framework for future studies of remote-control monitoring of disease activity, with great precision and minimal patient burden.
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Artrite Reumatoide/diagnóstico , Exercício Físico/fisiologia , Monitores de Aptidão Física/tendências , Aprendizado de Máquina/tendências , Espondilartrite/diagnóstico , Exacerbação dos Sintomas , Adulto , Artrite Reumatoide/fisiopatologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Reumatologia/métodos , Reumatologia/tendências , Espondilartrite/fisiopatologiaRESUMO
Adult-onset Still's disease (AoSD) is a rare but clinically well-known, polygenic, systemic autoinflammatory disease. Owing to its sporadic appearance in all adult age groups with potentially severe inflammatory onset accompanied by a broad spectrum of disease manifestation and complications, AoSD is an unsolved challenge for clinicians with limited therapeutic options. This Review provides a comprehensive insight into the complex and heterogeneous nature of AoSD, describing biomarkers of the disease and its progression and the cytokine signalling pathways that contribute to disease. The efficacy and safety of biologic therapeutic options are also discussed, and guidance for treatment decisions is provided. Improving the approach to AoSD in the future will require much closer cooperation between paediatric and adult rheumatologists to establish common diagnostic strategies, treatment targets and goals.
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Produtos Biológicos/uso terapêutico , Biomarcadores/metabolismo , Doença de Still de Início Tardio/tratamento farmacológico , Adulto , Produtos Biológicos/efeitos adversos , Ensaios Clínicos como Assunto , Citocinas/metabolismo , Progressão da Doença , Humanos , Índice de Gravidade de Doença , Transdução de Sinais , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/imunologiaRESUMO
BACKGROUND: Recent advances in knowledge of the pathogenesis of rheumatoid arthritis (RA) has led to promoting very early intervention. OBJECTIVES: To assess the efficacy of therapeutic interventions in preventing or delaying RA onset with a systematic literature review (SLR) and meta-analysis (MA). METHODS: The SLR aimed to include all reports of randomised controlled trials of disease-modifying antirheumatic drugs or glucocorticoids used in patients presenting genetic and/or environmental risk factors for RA and/or systemic autoimmunity associated with RA, and/or symptoms without clinical arthritis and/or unclassified arthritis and in patients with RA. We searched PubMed, EMBASE and Cochrane databases for English articles published from 2006 to 2016 using the keywords 'undifferentiated arthritis' or 'very early rheumatoid arthritis' with 'therapy' or 'treatment'. Main outcome was RA occurrence, defined as fulfilment of the 1987 ACR criteria. The MA was performed with RevMan with the Mantel-Haenszel method. RESULTS: Among 595 abstracts screened, 10 reports of trials were selected. The studies included 1156 patients, with mean symptom duration 16.2±12.6 weeks. The occurrence of RA was available for nine studies, assessing methylprednisolone, methotrexate, a tumour necrosis factor blocker, abatacept or rituximab. In the group arthralgia without arthritis (people at risk of RA), the MA of the two available studies did not show significant reduction in RA occurrence at week 52 or more (pooled OR 0.74, 95% CI 0.37 to 1.49). For people with undifferentiated arthritis, the MA of the seven available studies revealed significant risk reduction with OR 0.73(95% CI 0.56 to 0.97). CONCLUSIONS: This MA demonstrates that early therapeutic intervention may significantly reduce the risk of RA onset in this very first phase of the disease.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/prevenção & controle , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico por imagem , Progressão da Doença , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Radiografia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Indução de RemissãoRESUMO
INTRODUCTION: Adult-onset Still's disease (AOSD) is a rare systemic auto-inflammatory disorder in which management and treatment have considerably progressed over the past decade. Despite wide use of interleukin (IL)-1 or IL-6 inhibitors, serious complications remain possible. Areas covered: A comprehensive literature search in MEDLINE via Pubmed was performed to review AOSD's severe and sometimes life-threatening complications: reactive hemophagocytic lymphohystiocytosis, coagulation disorders, fulminant hepatitis, cardiac or pulmonary complications and amyloid A amyloidosis. Expert commentary: Early recognition and prompt management is essential to significantly decrease morbi-mortality. The key question is to determine whether the complication is related to the disease itself or related to or favored by (e.g. infection) the ongoing treatment. For all severe AOSD-related complications, high-dose corticosteroids and supportive measures remain the first-line treatment. In case of inadequate response, combination with IL-1 or IL-6 blockers is justified. Cyclosporine A and etoposide remain of interest, especially in case of reactive hemophagocytic lymphohysitocytosis. Plasma exchange may be useful in case of thrombotic microangiopathy. In the near future, new biologic or non-biologic drugs targeting IL-18 or other cytokines or kinases could be of help.
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Transtornos da Coagulação Sanguínea , Cardiopatias , Falência Hepática Aguda , Pneumopatias , Linfo-Histiocitose Hemofagocítica , Doença de Still de Início Tardio , Adulto , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/metabolismo , Transtornos da Coagulação Sanguínea/terapia , Feminino , Cardiopatias/etiologia , Cardiopatias/metabolismo , Cardiopatias/terapia , Humanos , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/metabolismo , Falência Hepática Aguda/terapia , Pneumopatias/etiologia , Pneumopatias/metabolismo , Pneumopatias/terapia , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/metabolismo , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Doença de Still de Início Tardio/complicações , Doença de Still de Início Tardio/metabolismo , Doença de Still de Início Tardio/terapiaRESUMO
OBJECTIVES: Fatigue is a significant issue in psoriatic arthritis. The objective was to assess the effect of biological disease modifying antirheumatic drugs and apremilast on fatigue in psoriatic arthritis randomised controlled trials and to compare this effect with the effect in the same trials, on pain, through a systematic literature review and meta-analysis. METHODS: A systematic literature review was performed up to January 2017 in PubMed, Embase and Cochrane databases. All randomized controlled trials in psoriatic arthritis of biological disease modifying antirheumatic drugs or apremilast, assessing fatigue (whatever the score used), were included. Data were collected by 2 assessors regarding levels of fatigue and pain at baseline and at the time point closest to 24 weeks after the treatment introduction. Pooled standardized mean differences were calculated using RevMan. RESULTS: After screening 295 publications, 7 randomised controlled trials were analysed: they pertained to adalimumab (n=2), certolizumab pegol (n=1), secukinumab (n=2), ustekinumab (n=1) and apremilast (n=1), compared to placebo. The studies included 2341 patients: weighted mean±standard deviation age: 48.6±1.3years, disease duration: 7.7±1.6years, 51.6% were females. Fatigue levels were high at baseline (Functional Assessment of Chronic Illness Therapy score: 28.7±2.4). The pooled standardized mean difference was, for fatigue -0.44 (95% confidence interval: -0.54, -0.35) and for pain, -0.62 (-0.73, -0.52). CONCLUSIONS: Biological disease modifying antirheumatic drugs and apremilast had a small effect on fatigue at 24 weeks in psoriatic arthritis randomized controlled trials and a higher effect on pain. These results are important to take into account in shared decision-making.
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Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/epidemiologia , Produtos Biológicos/uso terapêutico , Fadiga/epidemiologia , Qualidade de Vida , Adalimumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Artrite Psoriásica/diagnóstico , Bélgica , Certolizumab Pegol/uso terapêutico , Comorbidade , Fadiga/diagnóstico , Fadiga/tratamento farmacológico , Feminino , França , Humanos , Internacionalidade , Masculino , Medição da Dor , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Suíça , Talidomida/análogos & derivados , Resultado do TratamentoRESUMO
BACKGROUND: Physical activity can be tracked using mobile devices and is recommended in rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) management. The World Health Organization (WHO) recommends at least 150 min per week of moderate to vigorous physical activity (MVPA). OBJECTIVE: The objectives of this study were to assess and compare physical activity and its patterns in patients with RA and axSpA using an activity tracker and to assess the feasibility of mobile devices in this population. METHODS: This multicentric prospective observational study (ActConnect) included patients who had definite RA or axSpA, and a smartphone. Physical activity was assessed over 3 months using a mobile activity tracker, recording the number of steps per minute. The number of patients reaching the WHO recommendations was calculated. RA and axSpA were compared, using linear mixed models, for number of steps, proportion of morning steps, duration of total activity, and MVPA. Physical activity trajectories were identified using the K-means method, and factors related to the low activity trajectory were explored by logistic regression. Acceptability was assessed by the mean number of days the tracker was worn over the 3 months (ie, adherence), the percentage of wearing time, and by an acceptability questionnaire. RESULTS: A total of 157 patients (83 RA and 74 axSpA) were analyzed; 36.3% (57/157) patients were males, and their mean age was 46 (standard deviation [SD] 12) years and mean disease duration was 11 (SD 9) years. RA and axSpA patients had similar physical activity levels of 16 (SD 11) and 15 (SD 12) min per day of MVPA (P=.80), respectively. Only 27.4% (43/157) patients reached the recommendations with a mean MVPA of 106 (SD 77) min per week. The following three trajectories were identified with constant activity: low (54.1% [85/157] of patients), moderate (42.7% [67/157] of patients), and high (3.2% [5/157] of patients) levels of MVPA. A higher body mass index was significantly related to less physical activity (odds ratio 1.12, 95% CI 1.11-1.14). The activity trackers were worn during a mean of 79 (SD 17) days over the 90 days follow-up. Overall, patients considered the use of the tracker very acceptable, with a mean score of 8 out 10. CONCLUSIONS: Patients with RA and axSpA performed insufficient physical activity with similar levels in both groups, despite the differences between the 2 diseases. Activity trackers allow longitudinal assessment of physical activity in these patients. The good adherence to this study and the good acceptability of wearing activity trackers confirmed the feasibility of the use of a mobile activity tracker in patients with rheumatic diseases.
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Adult-onset Still's disease (AOSD) is a rare systemic auto-inflammatory disorder (SAID). Although the pathogenesis of the disease is complex and far from being fully understood, recent progresses in pathophysiological knowledge have paved the way to new diagnostic approaches. Indeed, AOSD diagnosis can be a real challenge, owing to its infrequency, and to the lack of specificity of the principal clinical features (high fever, arthralgia or arthritis, skin rash) and laboratory findings (elevated acute phase reactants, hyperleukocytosis≥10,000 cells/mm3 with neutrophils≥80%). None of these manifestations is disease-specific, so clinicians must first rule out neoplastic, infectious or inflammatory conditions. Besides these diagnostic difficulties, several other challenges remain. AOSD is very heterogeneous in terms of clinical presentation, evolution and severity. Thus, new biomarkers are required to assess: (i) disease activity; (ii) disease severity (through the identification of patients at risk of severe organ failure, and eventually of life-threatening complications, such as reactive haemophagocytic lymphohistiocytosis); (iii) disease evolution (which can be monophasic, relapsing, or progressive, with either systemic inflammation or chronic erosive arthritis); (iv) and treatment efficacy. The identification of new markers can only be done through a better understanding of the pathogenesis of the disease. After a short focus on the current AOSD pathophysiological knowledge, this article reviews the main biomarkers that have been proposed in the literature over the last few years.
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Ferritinas/sangue , Complexo Antígeno L1 Leucocitário/sangue , Proteínas S100/sangue , Doença de Still de Início Tardio/sangue , Adulto , Biomarcadores/sangue , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-18/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Doença de Still de Início Tardio/fisiopatologiaRESUMO
BACKGROUND: The evolution of rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) is marked by flares, although their frequency is unclear. Flares may impact physical activity. Activity can be assessed objectively using activity trackers. The objective was to assess longitudinally the frequency of flares and the association between flares and objective physical activity. METHODS: This prospective observational study (ActConnect) included patients with definite clinician-confirmed RA or axSpA, owning a smartphone. During 3 months, physical activity was assessed continuously by number of steps/day, using an activity tracker, and disease flares were self-assessed weekly using a specific flare question and, if relevant, the duration of the flare. The relationship between flares and physical activity for each week (time point) was assessed by linear mixed models. RESULTS: In all, 170/178 patients (91 patients with RA and 79 patients with axSpA; 1553 time points) were analysed: mean age was 45.5±12.4 years, mean disease duration was 10.3±8.7 years, 60 (35.3%) were men and 90 (52.9%) received biologics. The disease was well-controlled (mean Disease Activity Score 28: 2.3±1.2; mean Bath Ankylosing Spondylitis Disease Activity Index score: 3.3±2.1). Patients self-reported flares in 28.2%±28.1% of the weekly assessments. Most flares (78.9%±31.4%) lasted ≤3 days. Persistent flares lasting more than 3 days were independently associated with less weekly physical activity (p=0.03), leading to a relative decrease of 12%-21% and an absolute decrease ranging from 836 to 1462 steps/day. CONCLUSION: Flares were frequent but usually of short duration in these stable patients with RA and axSpA. Persistent flares were related to a moderate decrease in physical activity, confirming objectively the functional impact of patient-reported flares.
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Objectives: Mitochondrial DNA (mtDNA) contains sequestered damage-associated molecular patterns that might be involved in osteoimmunological pathogenesis of RA. Here, we aimed to investigate the cellular source of mtDNA and its role in RANK ligand (RANKL) expression by RA SF neutrophils. Methods: The gene expression signature of SF neutrophils was examined by proteomic quantitative analysis. Levels of mtDNA in circulating and SF neutrophils from RA patients and OA control subjects were assessed by real-time PCR. Purified neutrophils were challenged in vitro with Toll-like receptor agonists as well as mtDNA. RANKL expression by neutrophils was studied by flow cytometry. Results: SF neutrophils from RA patients displayed a gene expression signature of oxidative stress. This stress signature was associated with the release of mtDNA in SF as observed by a significant increase of mtDNA in the SF of RA patients compared with OA patients. mtDNA in RA SF was correlated with systemic inflammation as assessed by CRP concentrations. We also showed that mtDNA drives neutrophil RANKL expression to the same extent as Toll-like receptor agonists. Conclusion: Our data identify SF neutrophils as a cellular source of mtDNA that leads to a subsequent expression of RANKL. This highlights the important role of neutrophils in RA osteoimmunology.