Summary The human leucocyte antigen HLA‐B27 is strongly associated with ankylosing spondylitis, a form of seronegative inflammatory arthritis. In this study aspects related to several hypothesized mechanisms of disease pathogenesis have been investigated. Blood monocyte‐derived dendritic cells (DC) from a small patient cohort of 29 patients with ankylosing spondylitis and one with reactive arthritis, were compared with DC from 34 healthy control subjects, of whom four were found to be HLA‐B27 positive. The ability of HLA‐B27 to form heavy‐chain dimers reactive with monoclonal antibody HC10 was tested, along with the induction of endoplasmic reticulum (ER) stress, assessed by splicing xbp1 mRNA and immunoblotting of Immunoglobulin Binding Protein (BiP). Additionally, the protein expression levels of the ER resident aminopeptidase gene ERAP1 in patients with ankylosing spondylitis was also determined, following its recent identification as a novel disease‐associated gene. No significant difference was noted in the global levels of HC10‐reactive MHC class I dimers formed in either the patient or control DC populations. Stress on the ER, as determined by xbp1 mRNA splicing, was not detected but lower levels of BiP were observed in the DC from patients. Of further potential interest, in this patient cohort the expression of ERAP1 appeared to be higher in a number of patient DC samples when compared with controls, suggesting over‐expression of ERAP1 as a mechanism promoting ankylosing spondylitic pathogenesis.
Background/Aims Giant cell arteritis (GCA) is a systemic inflammatory disease of medium to large sized arteries. Diagnosis of GCA is a medical emergency due to the consequence of permanent blindness if not treated early with glucocorticoids. The objective of this audit was to assess the effectiveness of the GCA fast track clinic (FTC) in NHS Tayside. The current practice was compared with British Society of Rheumatology (BSR) standards. Methods This was a retrospective audit from March 2019 to May 2021. All patients referred with suspicion of GCA were included. Main outcomes measured were referral time, investigations and management. Data were collected through electronic records. Results 120 patients were included (median age 71 years; F71.7%). 35% of patients were diagnosed with GCA. Most common symptoms were headache (94.2%), jaw claudication (26.7%), visual symptoms (36.7%), PMR symptoms (21.7%), systemic symptoms (50%). As seen in Table 1, 50% with visual symptoms were seen by ophthalmology within 24 hours. 70.8% were seen by rheumatology within 24 hours. 89% were given steroids within 24 hours from suspicion. 80.8% were investigated with ultrasound or biopsy. Comparing with expected standards, provision of written information, advice on recurrence of symptoms, calculation of CRP, documentation of bone protection was achieved at 100%. Immediate follow-up time was 6 weeks. One patient lost vision while on steroids. Conclusion Early recognition and prompt management of GCA is crucial for a good prognosis. NHS Tayside’s FTC has allowed for quick evaluation for most patients within 24 hours and has improved prognosis in patients. Disclosure D. Subramanian: None. S. Bhat: None.
Objectives Although the painful and disabling features of early diffuse cutaneous systemic sclerosis (dcSSc) have an inflammatory basis and could respond to corticosteroids, corticosteroids are a risk factor for scleroderma renal crisis. Whether or not they should be prescribed is therefore highly contentious. Our aim was to examine safety and efficacy of moderate dose prednisolone in early dcSSc. Methods PRedSS set out as a Phase II, multicentre, double-blind randomised controlled trial, converted to open-label during the Covid-19 pandemic. Patients were randomised to receive either prednisolone (∼0.3 mg/kg) or matching placebo (or no treatment during open-label) for 6 months. Co-primary endpoints were the Health Assessment Questionnaire Disability Index (HAQ-DI) and modified Rodnan skin core (mRSS) at 3 months. Over 20 secondary endpoints included patient reported outcome measures reflecting pain, itch, fatigue, anxiety and depression, and helplessness. Target recruitment was 72 patients. Results Thirty-five patients were randomised (17 prednisolone, 18 placebo/control). The adjusted mean difference between treatment groups at 3 months in HAQ-DI score was -0.10 (97.5% CI -0.29–0.10), p= 0.254, and in mRSS -3.90 (97.5% CI -8.83–1.03), p= 0.070, both favouring prednisolone but not significantly. Patients in the prednisolone group experienced significantly less pain (p= 0.027), anxiety (p= 0.018) and helplessness (p= 0.040) than control patients at 3 months. There were no renal crises, but sample size was small. Conclusion PRedSS was terminated early primarily due to the Covid-19 pandemic, and so was underpowered. Therefore, interpretation must be cautious and results considered inconclusive, indicating the need for a further randomised trial. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT03708718
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