BACKGROUND AND PURPOSE—Systemic lupus erythematosus (SLE) increases stroke risk, but the mechanism is uncertain. This study aimed to determine the association between SLE and features on neuroimaging ...of cerebral small vessel disease (SVD), a risk factor for stroke.
METHODS—Consecutive patients attending a clinic for SLE were recruited. All patients underwent brain magnetic resonance imaging; had blood samples taken for markers of inflammation, endothelial dysfunction, cholesterol, and autoantibodies; and underwent cognitive and psychiatric testing. The data were compared with sex- and age-matched healthy controls and patients with minor stroke. Features of SVD were measured, a total SVD score calculated, and associations sought with vascular risk factors, cognition, SLE activity, and disease duration.
RESULTS—Fifty-one SLE patients (age48.8 years; SD14.3 years) had a greater total SVD score compared with healthy controls (1 versus 0; P<0.0001) and stroke patients (1 versus 0; P=0.02). There were higher perivascular spaces and deep white matter hyperintensity scores and more superficial brain atrophy in SLE patients versus healthy controls. Despite fewer vascular risk factors than similarly aged stroke patients, SLE patients had similar or more of some SVD features. The total SVD score was not associated with SLE activity, cognition, disease duration, or any blood measure.
CONCLUSIONS—In this data set, SLE patients had a high burden of SVD features on magnetic resonance imaging, particularly perivascular spaces. A larger longitudinal study is warranted to determine the causes of SVD features in SLE and clinical implications.
Objective
This work investigates network organisation of brain structural connectivity in systemic lupus erythematosus (SLE) relative to healthy controls and its putative association with lesion ...distribution and disease indicators.
Methods
White matter hyperintensity (WMH) segmentation and connectomics were performed in 47 patients with SLE and 47 healthy age-matched controls from structural and diffusion MRI data. Network nodes were divided into hierarchical tiers based on numbers of connections. Results were compared between patients and controls to assess for differences in brain network organisation. Voxel-based analyses of the spatial distribution of WMH in relation to network measures and SLE disease indicators were conducted.
Results
Despite inter-individual differences in brain network organization observed across the study sample, the connectome networks of SLE patients had larger proportion of connections in the peripheral nodes. SLE patients had statistically larger numbers of links in their networks with generally larger fractional anisotropy weights (i.e. a measure of white matter integrity) and less tendency to aggregate than those of healthy controls. The voxels exhibiting connectomic differences were coincident with WMH clusters, particularly the left hemisphere’s intersection between the anterior limb of the internal and external capsules. Moreover, these voxels also associated more strongly with disease indicators.
Conclusion
Our results indicate network differences reflective of compensatory reorganization of the neural circuits, reflecting adaptive or extended neuroplasticity in SLE.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Rheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these "at-risk" stages is not well described. This study ...assessed health-related quality of life (HRQoL), function, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) or RA.
Cross-sectional analysis of baseline Patient-Reported Outcome Measures (PROMs) was conducted in patients from the Birmingham Early Arthritis Cohort. HRQoL, function, depression and fatigue at presentation were assessed using EQ-5D, HAQ-DI, PHQ-9 and FACIT-F. PROMs were compared across CSA, UA and RA and with population averages from the HSE with descriptive statistics. Multivariate linear regression assessed associations between PROMs and clinical and sociodemographic variables.
Of 838 patients included in the analysis, 484 had RA, 200 had CSA and 154 had UA. Patients with RA reported worse outcomes for all PROMs than those with CSA or UA. However, "mean EQ-5D utilities were 0.65 (95%CI: 0.61 to 0.69) in CSA, 0.61 (0.56 to 0.66) in UA and 0.47 (0.44 to 0.50) in RA, which was lower than in general and older (≥ 65 years) background populations." In patients with CSA or UA, HRQoL was comparable to chronic conditions such as heart failure, severe COPD or mild angina. Higher BMI and older age (≥ 60 years) predicted worse depression (PHQ-9: -2.47 (-3.85 to -1.09), P < 0.001) and fatigue (FACIT-F: 5.05 (2.37 to 7.73), P < 0.001). Women were more likely to report worse function (HAQ-DI: 0.13 (0.03 to 0.21), P = 0.01) and fatigue (FACIT-F: -3.64 (-5.59 to -1.70), P < 0.001), and residents of more deprived areas experienced decreased function (HAQ-DI: 0.23 (0.10 to 0.36), P = 0.001), greater depression (PHQ-9: 1.89 (0.59 to 3.18), P = 0.004) and fatigue (FACIT-F: -2.60 (-5.11 to 0.09), P = 0.04). After adjustments for confounding factors, diagnostic category was not associated with PROMs, but disease activity and polypharmacy were associated with poorer performance across all PROMs.
Patient-reported outcomes were associated with disease activity and sociodemographic characteristics. Patients presenting with RA reported a higher health burden than those with CSA or UA, however HRQoL in the pre-RA groups was significantly lower than population averages.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Alemtuzumab is a monoclonal antibody targeted to CD52, an antigen of uncertain function on T and B lymphocytes. Alemtuzumab is an established treatment for active relapsing and ...remitting multiple sclerosis (MS). However, autoimmune disease (AID) is being increasingly recognised as a highly prevalent adverse effect of alemtuzumab treatment.
Methods
We describe a case of adult onset Still’s disease (AOSD) developing in a patient six months after alemtuzumab therapy, highlighting the need for awareness of the risk of AID in those who develop symptoms after alemtuzumab treatment, some of which can be potentially life-threatening.
Results
Our patient, a 37 year old female, was admitted to hospital with a three week history of fevers up to 39ºC, a flitting macular rash, sore throat and polyarthritis, neutrophils 35.2x109/L (2-7.5), ferritin 8349 ug/L (normal 15-150), ALP 151 U/L (25-105). She had a history of relapsing and remitting multiple sclerosis, that went into remission after treatment with alemtuzumab six months previously. Despite 72 hours of broad-spectrum intravenous antibiotics, fever and symptoms were unchanged. Immunology and microbiology tests were negative. CT scan of neck, chest abdomen and pelvis were unremarkable. A diagnosis of AOSD was made. She received prednisolone at 40mg daily and symptoms rapidly settled. By day three of prednisolone, ferritin had fallen to 3238, neutrophil count had halved, and ALP normalised. She continues on slow weaning of steroids and remains asymptomatic.
Conclusion
Alemtuzumab was approved in 2013 as a treatment for active relapsing and remitting MS. Treatment consists of two courses of ‘induction’ treatment 12 months apart, aiming to deplete T and B lymphocytes, with subsequent lymphocyte repopulation. Without requirement for continued ‘maintainance’ treatment, efficacy of alemtuzumab persists for years. The most common alemtuzumab associated AID are thyroid disease, nephropathies and immune thrombocytopenia. However, other AID has been reported, including sarcoidosis. To date, no reports exist describing AOSD post alemtuzumab therapy. Although lymphocyte reconstitution post alemtuzumab is thought to account for its therapeutic effects, this same reconstitution is postulated to contribute to AID. Baker et. al. postulated that rapid re-population of B lymphocytes and slower re-population of regulatory T lymphocytes may trigger B cell mediated AID. Further, rapid repopulation of immature B cells post alemtuzumab is associated with raised serum B cell activating factor (BAFF), which remains elevated for at least a year post treatment. BAFF has been recognised in multiple animal studies to be associated with antibody mediated AID. The hypothesis that B cells play a key role in alemtuzumab related AID may be supported by the success of rituximab in treating 2 cases of alemtuzumab associated AID. The possible critical role of B cells in the pathogenesis of alemtuzumab related AID could indicate a future treatment strategy for such AID.
Disclosures
N. Narayan None. G. Mazibrada None. N. Amft None.
Abstract
Objectives
Infection exerts a major burden in ANCA-associated vasculitis (AAV), however, its precise extent and nature remains unclear. In this national study we aimed to longitudinally ...quantify, characterize and contextualize infection risk in AAV.
Methods
We conducted a multicentre matched cohort study of AAV. Complementary data on infections were retrieved via data linkage with the population-based Scottish microbiological laboratory, hospitalization and primary care prescribing registries.
Results
A total of 379 AAV patients and 1859 controls were followed up for a median of 3.5 years (interquartile range 1.9–5.7). During follow-up, the proportions of AAV patients with at least one laboratory-confirmed infection, severe infection and primary care antibiotic prescription were 55.4%, 35.6% and 74.6%, respectively. The risk of infection was higher in AAV than in matched controls {laboratory-confirmed infections: incidence rate ratio IRR 7.3 95% confidence interval (CI) 5.6, 9.6; severe infections: IRR 4.4 95% CI 3.3, 5.7; antibiotic prescriptions: IRR 2.2 95% CI 1.9, 2.6}. Temporal trend analysis showed that AAV patients remained at a higher risk of infections throughout the follow-up period, especially year 1. Although the Escherichia genus was the most commonly identified pathogen (16.6% of AAV, 5.5% of controls; P < 0.0001), AAV patients had the highest risk for Herpes IRR 12.5 (95% CI 3.7, 42.6) and Candida IRR 11.4 (95% CI 2.4, 55.4).
Conclusion
AAV patients have up to seven times higher risk of infection than the general population and the overall risk remains significant after 8 years of follow-up. The testing of enhanced short- to medium-term prophylactic antibiotic regimes should be considered.
According to the current model for tissue-specific homing, specificity is conferred by the selective recruitment of lymphocyte populations from peripheral blood, based on their expression of ...chemokine and adhesion receptors (endothelial selection). In this study, we provide evidence for an alternative stromal induction mechanism that operates in chronic inflammation. We show that the human rheumatoid synovial microenvironment directly induces functional inflammatory (CCR5 and CXCR3) and constitutive (CCR7 and CXCR4) chemokine receptors on infiltrating CD4(+) T cells. Expression of the corresponding inflammatory chemokine ligands (CCL5 and CXCL11) was confined to stromal areas in the synovium. However, expression of the constitutive ligands (CCL19 and CXCL12) was inappropriately high on both vascular and lymphatic endothelium, suggesting that the vascular to lymphatic chemokine gradient involved in lymphatic recirculation becomes subverted in the rheumatoid synovium. These results challenge the view that leukocyte trafficking is regulated solely by selective recruitment of pre-existing chemokine receptor-positive cells from peripheral blood, by providing an alternative explanation based on aberrant lymphocyte retention and compromised lymphatic return.
Abstract
Objectives
The value of US-defined tenosynovitis in predicting the persistence of inflammatory arthritis is not well described. In particular, the predictive utility of US-defined ...tenosynovitis of larger tendons is yet to be reported. We assessed the value of US-defined tenosynovitis alongside US-defined synovitis and clinical and serological variables in predicting persistent arthritis in an inception cohort of DMARD-naïve patients with early arthritis.
Methods
One hundred and fifty DMARD-naïve patients with clinically apparent synovitis of one or more joints and a symptom duration of ≤3 months underwent baseline clinical, laboratory and US (of 19 bilateral joints and 16 bilateral tendon compartments) assessments. Outcomes were classified as persistent or resolving arthritis after 18 months’ follow-up. The predictive value of US-defined tenosynovitis for persistent arthritis was compared with those of US-defined synovitis, and clinical and serological variables.
Results
At 18 months, 99 patients (66%) had developed persistent arthritis and 51 patients (34%) had resolving disease. Multivariate logistic regression analysis showed that US-detected digit flexor tenosynovitis odds ratio (OR): 6.6, 95% CI: 2.0 , 22.1, P = 0.002 provided independent predictive data for persistence over and above the presence of US-detected joint synovitis and RF antibodies. In the RF/ACPA-negative subcohort, US-defined digit flexor tenosynovitis remained a significant predictive variable (OR: 4.7, 95% CI: 1.4, 15.8, P = 0.012), even after adjusting for US-defined joint synovitis.
Conclusion
US-defined tenosynovitis provided independent predictive data for the development of persistent arthritis. The predictive role of US-defined digit flexor tenosynovitis should be further assessed; investigators should consider including this tendon site as a candidate variable when designing imaging-based predictive algorithms for persistent inflammatory arthritis development.
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