Berit Schiøttz-Christensen

Prognostic Significance of Magnetic Resonance Imaging Changes of the Sacroiliac Joints in Spondyloarthritis – A Followup Study

Objective. To evaluate the prognostic significance of sacroiliac joint (SIJ) changes by magnetic resonance imaging (MRI) based on 2–7 years of followup of patients with axial spondyloarthritis (SpA). Methods. Ninety-four patients (50 women, 44 men) with axial SpA obtained MRI of the SIJ from 1998–2004. They were examined at followup after 25–95 months (mean 51), including MRI and radiography of the SIJ and the spine. The Danish scoring method was used to quantify the activity and chronic SIJ changes by MRI. The activity score included subchondral edema and/or enhancement, while chronic changes encompassed erosions and subchondral fatty marrow deposition (FMD). Results. The MR score values for chronic SIJ changes increased significantly during followup, and were most pronounced in HLA-B27-positive patients and patients fulfilling the modified New York criteria for ankylosing spondylitis (AS) at followup. SIJ activity scores ≥ 2, total chronic scores ≥ 1, erosion scores ≥ 1, and FMD scores ≥ 4 at baseline were significantly related to progression of chronic SIJ changes. Activity score values ≥ 3 at baseline had a sensitivity of 0.83, specificity of 0.75, and accuracy of 0.80 in relation to the presence of AS at followup. The similar values for total chronic SIJ scores ≥ 4 at baseline were 0.86, 0.75, and 0.82, respectively, and for erosion scores ≥ 2 they were 0.88, 0.75, and 0.83. Conclusion. The occurrence of manifest SIJ activity by MRI or chronic changes at baseline was related to progression of chronic changes and the presence of AS at followup.

Postural balance in low back pain patients: criterion-related validity of centre of pressure assessed on a portable force platform.

IntroductionAltered postural control has been observed in low back pain (LBP) patients. They seem to be more dependent on vision when standing. The objective of the study was to determine concurrent and predictive validity of measures of postural stability in LBP patients.Materials and methodsCentre of Pressure (CoP) measurements were tested against pain, fear of pain, and physical function. Velocity, anterior–posterior displacement, and the Romberg Ratio obtained on a portable force platform were used as measures of postural stability.ResultsBaseline and 12-week follow-up results of 97 LBP patients were evaluated. The correlations between CoP measurements and pain, fear of pain, and physical function were poor. There were no significant differences in CoP measurements between patients with no change or deterioration and patients with improvement in pain and back-specific function.ConclusionThis first study of concurrent and predictive validity of postural balance in LBP patients revealed no association between CoP measures and pain, fear of pain, and physical function.

Predictors of vocational prognosis after herniated lumbar disc: a two-year follow-up study of 2039 patients diagnosed at hospital.

Study Design. A register study with 2 years of follow up. Objective. To identify predictors of an unfavorable vocational prognosis after hospital contact for herniated lumbar disc (HLD). Summary of Background Data. There is sparse information about vocational prognosis among HLD patients diagnosed at hospital. Methods. We followed all in- and outpatients diagnosed with HLD at a Danish University Hospital 2001 to 2005 eligible for the labor market in the Danish National Register on Public Transfer Payments (n = 2039). Clinical data were obtained from the Danish National Patient Register. The outcome measure was unfavorable vocational prognosis defined as less than 40 weeks of employment within the second year after hospital contact. Cox proportional hazards models were used. Results. Altogether 41.8% had an unfavorable vocational prognosis. The outcome was associated with unskilled work Hazard Ratio (HR) 2.1 (95% confidence interval [CI] = 1.5–2.8), skilled work HR 1.9 (CI = 1.3–2.7), and semi academic work HR 1.5 (CI = 1.1–2.0) as compared with academic work and less than 40 weeks of employment within year two before hospital contact HR 2.1 (CI = 1.9–2.5). Further negative prognostic factors were lumbar fusion alone HR 1.4 (CI = 1.1–1.8) and in combination with discectomy HR 1.6 (CI = 1.2–2.2) as compared with nonsurgical treatment, ethnicity other than Danish HR 1.55 (CI = 1.2–1.8), and female gender HR 1.2 (CI = 1.1–1.4). Discectomy, age, and year of inclusion were not associated with the outcome. Conclusion. The risk of an unfavorable vocational prognosis after hospital contact for HLD was substantial. Nonacademic work and less than 40 weeks of employment within year two before hospital contact were the strongest prognostic factors, but also lumbar fusion alone and in combination with discectomy, ethnicity, and gender had a negative influence. There seems to be a need for actions addressing these patient categories to avoid long-term sick leave and premature withdrawal from the labor market.

Toll‐like receptor 2 and 4 induced interleukin‐19 dampens immune reactions and associates inversely with spondyloarthritis disease activity

Spondyloarthritis (SpA) is a group of immune mediated inflammatory diseases affecting joints, gut, skin and entheses. The inflammatory process involves activation of Toll‐like receptor (TLR)‐2 and TLR‐4 and production of cytokines and chemokines such as monocyte chemoattractant protein 1 (CCL2/MCP‐1). This proinflammatory chemokine recruits monocytes to sites of inflammation and is central in the development of several immune‐mediated inflammatory diseases. Interleukin (IL)‐19 is a member of the IL‐10 family of cytokines. IL‐19‐deficient mice are more susceptible to innate‐mediated colitis and develop more severe inflammation in response to injury. In this work, we studied inducers of IL‐19 production and effect of IL‐19 on the production of CCL2/MCP‐1 and proinflammatory cytokines in peripheral blood mononuclear cells (PBMCs) from healthy controls (HCs) and in PBMCs and synovial fluid mononuclear cells (SFMCs) from SpA patients. Further, we measured IL‐19 in plasma from HCs and in plasma and synovial fluid from SpA patients. Constitutive IL‐19 expression was present in both PBMCs and SFMCs and the secretion of IL‐19 was increased by TLR‐2 and TLR‐4 ligands. Neutralizing IL‐19 in HC PBMCs and SpA SFMCs resulted in increased production of CCL‐2/MCP‐1. IL‐19 concentrations were decreased in synovial fluid compared with plasma and associated inversely with disease activity in SpA. SpA SFMCs produced less IL‐19 in response to LPS compared with HC PBMCs. These findings indicate that IL‐19 production is diminished in SpA. Taken together, impaired IL‐19 control of the innate immune system might be involved in the pathogenesis of SpA.

SpineData – a Danish clinical registry of people with chronic back pain

Background Large-scale clinical registries are increasingly recognized as important resources for quality assurance and research to inform clinical decision-making and health policy. We established a clinical registry (SpineData) in a conservative care setting where more than 10,000 new cases of spinal pain are assessed each year. This paper describes the SpineData registry, summarizes the characteristics of its clinical population and data, and signals the availability of these data as a resource for collaborative research projects. Methods The SpineData registry is an Internet-based system that captures patient data electronically at the point of clinical contact. The setting is the government-funded Medical Department of the Spine Centre of Southern Denmark, Hospital Lillebaelt, where patients receive a multidisciplinary assessment of their chronic spinal pain. Results Started in 2011, the database by early 2015 contained information on more than 36,300 baseline episodes of patient care, plus the available 6-month and 12-month follow-up data for these episodes. The baseline questionnaire completion rate has been 93%; 79% of people were presenting with low back pain as their main complaint, 6% with mid-back pain, and 15% with neck pain. Collectively, across the body regions and measurement time points, there are approximately 1,980 patient-related variables in the database across a broad range of biopsychosocial factors. To date, 36 research projects have used data from the SpineData registry, including collaborations with researchers from Denmark, Australia, the United Kingdom, and Brazil. Conclusion We described the aims, development, structure, and content of the SpineData registry, and what is known about any attrition bias and cluster effects in the data. For epidemiology research, these data can be linked, at an individual patient level, to the Danish population-based registries and the national spinal surgery registry. SpineData also has potential for the conduct of cohort multiple randomized controlled trials. Collaborations with other researchers are welcome.

Increased Levels of IgG Antibodies against Human HSP60 in Patients with Spondyloarthritis

Spondyloarthritis (SpA) comprises a heterogeneous group of inflammatory diseases, with strong association to human leukocyte antigen (HLA)-B27. A triggering bacterial infection has been considered as the cause of SpA, and bacterial heat shock protein (HSP) seems to be a strong T cell antigen. Since bacterial and human HSP60, also named HSPD1, are highly homologous, cross-reactivity has been suggested in disease initiation. In this study, levels of antibodies against bacterial and human HSP60 were analysed in SpA patients and healthy controls, and the association between such antibodies and disease severity in relation to HLA-B27 was evaluated. Serum samples from 82 patients and 50 controls were analysed by enzyme-linked immunosorbent assay (ELISA) for immunoglobulin (Ig)G1, IgG2, IgG3 and IgG4 antibodies against human HSP60 and HSP60 from Chlamydia trachomatis, Salmonella enteritidis and Campylobacter jejuni. Disease severity was assessed by the clinical scorings Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI). Levels of IgG1 and IgG3 antibodies against human HSP60, but not antibodies against bacterial HSP60, were elevated in the SpA group compared with the control group. Association between IgG3 antibodies against human HSP60 and BASMI was shown in HLA-B27+ patients. Only weak correlation between antibodies against bacterial and human HSP60 was seen, and there was no indication of cross-reaction. These results suggest that antibodies against human HSP60 is associated with SpA, however, the theory that antibodies against human HSP60 is a specific part of the aetiology, through cross-reaction to bacterial HSP60, cannot be supported by results from this study. We suggest that the association between elevated levels of antibodies against human HSP60 and disease may reflect a general activation of the immune system and an increased expression of human HSP60 in the synovium of patients with SpA.

Increased interleukin (IL)-20 and IL-24 target osteoblasts and synovial monocytes in spondyloarthritis: IL-20 and IL-24 in SpA

The pathogenesis of spondyloarthritis (SpA) involves activation of the innate immune system, inflammation and new bone formation. The two cytokines interleukin (IL)‐20 and IL‐24 have been shown to link innate immune activation and tissue homeostasis. We hypothesized that these two cytokines are secreted as part of activation of the innate immune system and affect bone homeostasis in SpA. IL‐20 and IL‐24 were measured in plasma from axial SpA patients (n = 83). Peripheral SpA patients (n = 16) were included for in‐vitro cell culture studies. The plasma IL‐20 and IL‐24 levels were increased in SpA patients compared with healthy controls (HCs) by 57 and 83%, respectively (both P < 0·0001). The Toll‐like receptor 4‐induced secretion of the two cytokines was greater in SpA peripheral blood mononuclear cells (PBMCs) compared with HC PBMCs. IL‐20 and IL‐24 increased the production of monocyte chemoattractant protein‐1 by activated SpA synovial fluid monocytes, decreased the production of Dickkopf‐1 by SpA fibroblast‐like synovial cells and induced mineralization in human osteoblasts. Taken together, our findings indicate disease‐aggravating functions of IL‐20 and IL‐24 in SpA.

Increased IL‐20 and IL‐24 target osteoblasts and synovial monocytes in spondyloarthritis

The pathogenesis of spondyloarthritis (SpA) involves activation of the innate immune system, inflammation and new bone formation. The two cytokines interleukin (IL)‐20 and IL‐24 have been shown to link innate immune activation and tissue homeostasis. We hypothesized that these two cytokines are secreted as part of activation of the innate immune system and affect bone homeostasis in SpA. IL‐20 and IL‐24 were measured in plasma from axial SpA patients (n = 83). Peripheral SpA patients (n = 16) were included for in‐vitro cell culture studies. The plasma IL‐20 and IL‐24 levels were increased in SpA patients compared with healthy controls (HCs) by 57 and 83%, respectively (both P < 0·0001). The Toll‐like receptor 4‐induced secretion of the two cytokines was greater in SpA peripheral blood mononuclear cells (PBMCs) compared with HC PBMCs. IL‐20 and IL‐24 increased the production of monocyte chemoattractant protein‐1 by activated SpA synovial fluid monocytes, decreased the production of Dickkopf‐1 by SpA fibroblast‐like synovial cells and induced mineralization in human osteoblasts. Taken together, our findings indicate disease‐aggravating functions of IL‐20 and IL‐24 in SpA.

Validity and completeness of rheumatoid arthritis diagnoses in the nationwide DANBIO clinical register and the Danish National Patient Registry

Objectives In Denmark, patients with rheumatoid arthritis (RA) are registered in the nationwide clinical DANBIO quality register and the Danish National Patient Registry (DNPR). The aim was to study the validity of the RA diagnosis and to estimate the completeness of relevant RA cases in each registry. Study design and setting Patients registered for the first time in 2011 with a diagnosis of RA were identified in DANBIO and DNPR in January 2013. For DNPR, filters were applied to reduce false-positive cases. The diagnosis was verified by a review of patient records. We calculated the positive predictive values (PPVs) of the RA diagnosis registrations in DANBIO and DNPR, and estimated the registry completeness of relevant RA cases for both DANBIO and DNPR. Updated data from 2011 to 2015 from DANBIO were retrieved to identify patients with delayed registration, and the registry completeness and PPV was recalculated. Results We identified 1,678 unique patients in DANBIO or in DNPR. The PPV (2013 dataset) was 92% in DANBIO and 79% in DNPR. PPV for DANBIO on the 2015 update was 96%. The registry completeness of relevant RA cases was 43% in DANBIO, increasing to 91% in the 2015 update and 90% in DNPR. Conclusion DANBIO held a high proportion of true RA cases (96%) and was found to be superior to the DNPR (79%) with regard to the validity of the diagnosis. Both registries were estimated to have a high completeness of RA cases treated in hospital care (~90%).

The effect on physical performance of a functional assessment and immediate rehabilitation of acutely admitted elderly patients with reduced functional performance: the design of a randomised clinical trial

Introduction Illness and hospitalisation, even of short duration, pose separate risks for permanently reduced functional performance in elderly medical patients. Functional assessment in the acute pathway will ensure early detection of declining performance and form the basis for mobilisation during hospitalisation and subsequent rehabilitation. For optimal results rehabilitation should begin immediately after discharge.The aim of this study is to investigate the effect of a systematic functional assessment in the emergency department (ED) of elderly medical patients with reduced functional performance when combined with immediate postdischarge rehabilitation. Method and analysis The study is a two-way factorial randomised clinical trial. Participants will be recruited among patients admitted to the ED who are above 65 years of age with reduced functional performance. Patients will be randomly assigned to one of four groups: (1) functional assessment and immediate rehabilitation; (2) functional assessment and rehabilitation as usual; (3) assessment as usual and immediate rehabilitation; (4) assessment and rehabilitation as usual. Primary outcome 30 s chair-stand test administered at admission and 3 weeks after discharge. Ethics and dissemination The study has been approved by the Regional Scientific Ethical Committees of Southern Denmark in February 2014. The study findings will be published in peer-reviewed journals and presented at national and international conferences. Trial registration number: ClinicalTrials.gov Identifier: NCT02062541.