Introduction: Enthesitis is a hallmark of psoriatic disease, but its clinical assessment is problematic in terms of diagnostic sensitivity and overlap with other comorbid conditions. Ultrasound is a useful tool that can give a more detailed assessment of enthesitis. Research demonstrates that those with persistent ultrasound entheseal disease are at risk of progressive articular damage. With limited data to guide choice between biologic therapy for psoriatic arthritis (PsA) patients, we wanted to assess the response of ultrasound-confirmed enthesitis to different forms of biologic therapies and study its utility in making more informed decisions. Methods: This was an open label observational study including patients aged ⩾18 years, who fulfil the classification criteria for PSA (CASPAR) and were due to commence on their first biologic therapy. The primary outcome was the change in MAdrid Sonographic Enthesitis Index (MASEI) score at 16 weeks of treatment. The MASEI score was also modified to assess the active elementary lesions (ActiveMASEI). Results: In all, 80 PsA patients were enrolled with 75 patients completing the study [secukinumab n = 23 and tumour necrosis factor inhibitor (TNFi) n = 52]. The mean reduction in MASEI score after 16 weeks of treatment was 3.42 with TNFi versus 1.74 with secukinumab ( p = 0.097). There was a significant difference in the change in the MASEIActive score for TNFi versus secukinumab (4.37 versus 2.26; p = 0.030) and this difference was more pronounced when only power Doppler signal within 2 mm of the enthesis insertion was included (4.37 versus 2.00; p = 0.007). Clinical outcomes were similar for both classes of biologic apart from a significant reduction in regards to the Dermatology Life Quality Index and Psoriasis Area and Severity Index score with secukinumab versus TNFi. Conclusions: We have for the first time compared the effect of ultrasound-confirmed enthesitis between different forms of biologic therapies for PsA. We have seen an overall improvement in entheseal scores for both classes of medications and demonstrated a larger reduction in active entheseal disease for TNFi versus secukinumab that merits further exploration. Keywords biologic therapy , enthesitis , psoriasis , psoriatic arthritis , ultrasound

Abstract Background/Aims Rheumatoid vasculitis (RV) is an extra-articular manifestation of rheumatoid arthritis (RA) which is usually seen in long-standing severe disease, affecting approximately 1-5% of the patient population. It involves small- to medium-sized arteries and has a high mortality rate of 40% at 5 years post-diagnosis. Methods In this report we describe a case of a 58-year-old male with no significant past medical history other than previous heavy smoking, who presented with a several week history of weakness, paraesthesia, numbness and pain affecting both hands and feet. He had also experienced weight loss of 12lbs in a short period, night sweats, and arthralgia in his hands, along with a six-week history of Raynaud’s phenomenon. Results Examination revealed nailfold infarcts but there was no evidence of synovitis and this was subsequently confirmed to be absent on ultrasound of the small joints of the hands and feet. Investigations showed: CRP 79, ESR 52, rheumatoid factor >130 and anti-CCP >733. Cryoglobulins were not detected, complement was normal and neuropathy screen bloods including viral and autoantibody screens were otherwise unremarkable. During admission he developed nodular lesions over the extensor aspect of his forearms bilaterally, consistent with rheumatoid nodules. These evolved over a period of four days. He also developed a vasculitic rash over the medial malleolus of his left foot. Nerve conduction studies demonstrated mononeuritis multiplex and PET CT showed evidence of small vessel vasculitis. CT chest, abdomen and pelvis identified a 3cm hypodense lesion within the tail of the pancreas, subsequently found to be a benign lymphoepithelial cyst on biopsy. Treatment with intravenous methylprednisolone for three days resulted in a rapid improvement in both motor and sensory function of his limbs. On discharge, he was commenced on oral methotrexate and a reducing course of prednisolone, starting at 30mg daily. The clinical picture was highly suggestive of RV in the absence of an established inflammatory arthritis. When reviewed three months post-discharge he reported continuing improvement of his symptoms; the nodules had regressed in size and almost disappeared. Conclusion To our knowledge, only seven cases have been reported in the literature of a patient with RV at initial diagnosis of RA and two cases in which a diagnosis of RV preceded the diagnosis of RA. Due to its high mortality and morbidity we would like to increase awareness amongst clinicians of this unusual vasculitic form of clinical presentation of RA. Disclosure D.A.J. Cromie: None. S.K. Stewart: None. G.D. Wright: None.

Introduction:Enthesitis is a hallmark of psoriatic disease, but its clinical assessment is problematic in terms of diagnostic sensitivity and overlap with other comorbid conditions. Ultrasound is a useful tool that can give a more detailed assessment of enthesitis. Research demonstrates that those with persistent ultrasound entheseal disease are at risk of progressive articular damage. With limited data to guide choice between biologic therapy for psoriatic arthritis (PsA) patients, we wanted to assess the response of ultrasound-confirmed enthesitis to different forms of biologic therapies and study its utility in making more informed decisions. Methods:This was an open label observational study including patients aged ⩾18 years, who fulfil the classification criteria for PSA (CASPAR) and were due to commence on their first biologic therapy. The primary outcome was the change in MAdrid Sonographic Enthesitis Index (MASEI) score at 16 weeks of treatment. The MASEI score was also modified to assess the active elementary lesions (ActiveMASEI). Results:In all, 80 PsA patients were enrolled with 75 patients completing the study [secukinumab n = 23 and tumour necrosis factor inhibitor (TNFi) n = 52]. The mean reduction in MASEI score after 16 weeks of treatment was 3.42 with TNFi versus 1.74 with secukinumab (p = 0.097). There was a significant difference in the change in the MASEIActive score for TNFi versus secukinumab (4.37 versus 2.26; p = 0.030) and this difference was more pronounced when only power Doppler signal within 2 mm of the enthesis insertion was included (4.37 versus 2.00; p = 0.007). Clinical outcomes were similar for both classes of biologic apart from a significant reduction in regards to the Dermatology Life Quality Index and Psoriasis Area and Severity Index score with secukinumab versus TNFi. Conclusions:We have for the first time compared the effect of ultrasound-confirmed enthesitis between different forms of biologic therapies for PsA. We have seen an overall improvement in entheseal scores for both classes of medications and demonstrated a larger reduction in active entheseal disease for TNFi versus secukinumab that merits further exploration.

Abstract Introduction/Background Rheumatic diseases can manifest as a paraneoplastic phenomenon. They can be seen during the course of neoplastic disease, precede the diagnosis, appear simultaneously or occur after the diagnosis of malignancy. Overall, paraneoplastic rheumatic syndromes are rare. It is however important to be aware of this phenomenon as the signs and symptoms of the rheumatic syndrome will usually subside with treatment of the underlying malignant disease. Furthermore, reappearance of symptoms may suggest cancer relapse. Description/Method 51 year old woman with no significant past medical history was referred by her General Practicioner with 6-week history of pain and stiffness in hands, arms and legs. There was also associated 4-week history of change in bowel habit (diarrhoea and faecal incontinence). Clinical examination revealed skin thickening proximal to elbows and knees, sclerodactyly, facial telangiectasia as well as tendon friction rubs in lower limbs. There was also a mass palpable on digital rectal examination. Investigations revealed that the patient had new iron deficiency anaemia and mildly raised carcinoembryonic antigen. Anti-RNA polymerase III antibody returned positive. CT of chest, abdomen and pelvis suggested tumour involving the anus and lower rectum with metastatic lymphadenopathy. Those findings were also confirmed on subsequent MRI pelvis and PET CT. She underwent anal biopsy, examination under anaesthesia and formation of loop colostomy. Histopathology results confirmed poorly differentiated squamous carcinoma. Patient was then reviewed by oncology and discussed at multidisciplinary meeting. She was commenced on palliative chemotherapy (paclitaxel and carboplatin). After the first session she became severely anaemic and developed acute renal failure. She passed away approximately three months after initial referral to rheumatology. Discussion/Results This patient was diagnosed with paraneoplastic diffuse systemic sclerosis in association with ano-rectal tumour. Unfortunately at the time of diagnosis the disease was metastatic therefore the only treatment option available was palliative rather than curative. Paraneoplastic rheumatic syndromes are rare. The signs and symptoms are secondary to the presence of malignancy. They may be induced by the substances that are secreted by the tumour or the immune system’s response to the malignant cells. Usually once patient recovers from the neoplastic disease the rheumatic disease signs/symptoms subside. In our patient’s history there were a number of features which raised the possibility of paraneoplastic aetiology. These included: sudden onset and rapid progression of clinical symptoms, late onset of disease (after 50 years of age), family history of cancer (dad had prostate cancer), new iron deficiency anaemia as well as the presence of anti-RNA polymerase III antibodies. This antibody is linked with cancer-associated systemic sclerosis. Patients who are positive have shorter cancer-scleroderma interval. Anti-RNA polymerase III antibody is unique to scleroderma and is not found in cancer patients without scleroderma. Key learning points/Conclusion The key learning point from this case was not to forget the paraneoplastic aetiology in patients who present with rheumatic syndromes. In particular if the symptoms are of sudden onset or are progressing rapidly/responding poorly to therapy. There is only a small number of cases reported in literature of paraneoplastic systemic sclerosis. Furthermore, the importance of anti-RNA polymerase III antibody testing in scleroderma patients. If positive, it is important to be aware that those patients have >4-fold increased risk of cancer occurring within 2 years of scleroderma onset. It is therefore vital to look for any signs/symptoms during their routine follow-up appointments at rheumatology clinics.

A 51-year-old female presented with a 6-week history of pain and stiffness in hands and legs. She also reported a 4-week history of diarrhoea and faecal incontinence. Clinical examination revealed skin thickening proximal to both elbows and knees (Fig. 1A–C), sclerodactyly and tendon friction rubs. Palpable mass was felt on digital rectal examination. Laboratory findings were normal except for iron deficiency anaemia and mildly raised carcinoembryonic antigen. Anti-RNA polymerase III antibody returned positive. CT chest abdomen and pelvis was suggestive of tumour involving the anus and lower rectum with metastatic adenopathy (Fig. 1D). MRI of the pelvis and rectum showed an anal tumour invading the posterior wall of the vagina. These findings were confirmed on PET scan. The patient underwent examination under anaesthesia, anal biopsy and formation of loop colostomy. Histology confirmed poorly differentiated squamous cell carcinoma (Fig. 1E). Following multidisciplinary team discussion, she...

Disease activity in rheumatoid arthritis (RA) is influenced by activation of circulating and synovial immune cells. Regulatory T cells (Tregs) and monocytes are key cells that drive inflammation in RA. This study investigated if a relationship exists between disease activity in RA and circulating Treg and monocyte numbers and phenotypes. A potential sialic acid (Sia) mediated link between Tregs and monocytes was also probed in vitro. Peripheral blood mononuclear cells (PBMCs) were isolated from RA patient (n = 62) and healthy control (n = 21) blood using density gradient separation. Flow cytometry was used to count and phenotype Treg and monocyte subsets, and to sort healthy control Tregs for Sia cell culture experiments. The effects of Sia on activated Treg FoxP3 and NFκB expression was assessed by flow cytometry and concentrations of secreted TNFα, IL-10 and IFNγ determined by ELISA. High disease activity RA patients who were unresponsive to disease modifying anti-rheumatic drugs (n = 31), have significantly lower relative numbers (percentages) of CD4+CD25+CD127− Tregs (p < 0.01) and memory CD45RA−FoxP3+ Tregs (p < 0.01), compared to low disease activity responders (n = 24). Relative numbers of non-classical CD169+ monocytes are associated with disease activity in RA (p = 0.012). Sia reduced Treg expression of FoxP3, NFκB and cytokines in vitro. A strong association has been identified between non-classical CD169+ monocytes and post-treatment disease activity in RA. This study also indicates that Sia can reduce Treg activation and cytokine release. We postulate that such a reduction could be mediated by interaction with sialyted proteins captured by CD169+ monocytes.

The symptoms of a rheumatic disease may also be a sign of a proliferative process. These include conditions that present with skin and vascular changes such as systemic sclerosis and Raynaud’s phenomenon with peripheral ischaemia and ulceration. Furthermore, the less common conditions – erythromelalgia or palmar fasciitis with polyarthritis may also accompany cancer. In this article, we discuss the association of diffuse systemic sclerosis with anorectal tumor, palmar fasciitis and polyarthritis with ovarian cancer, erythromelalgia with underlying ovarian malignancy and Raynaud’s phenomenon and digital ischemia associated with renal carcinoma. Based on the literature review on this topic we highlighted the importance of recognizing paraneoplastic syndromes at an early stage. This is a crucial point in the adequate management of a patient. Many of the paraneoplastic symptoms of rheumatic and other described conditions may regress with the management of the underlying malignancy.

Abstract Objective Psoriatic nail disease is more common in PsA than in isolated skin psoriasis (PsO). The nail is closely integrated to the DIP joint entheses. US data have shown that those patients with nail disease in PsO are more likely to have systemic enthesitis. We examined whether there was a relationship between nail disease, DIP enthesitis and systemic enthesitis in established PsA. Methods Forty-six PsA participants with nail disease underwent US scanning of the nail unit and the DIP entheses along with peripheral entheseal sites according to the Madrid sonographic enthesitis index (MASEI). Results At the finger level, there was a mild to moderate correlation between nail US changes and both clinical nail disease and DIP enthesis changes (DIP US) [Spearman correlation (rS) = 0.30, P < 0.001 and rS = 0.16, P < 0.001, respectively]. At the patient level, there was a moderate correlation between the nail US score and nail psoriasis severity index score and DIP US (rS = 0.33, P = 0.024 and rS = 0.43, P = 0.003, respectively). At the patient level, there was also a positive correlation between a higher nail US score and the active peripheral enthesitis score (MASEI-active) (rS = 0.35, P = 0.018). When power Doppler was part of nail US score, similar results were demonstrated at both the finger and patient levels. Conclusion This study has demonstrated the utility of nail US imaging and the close relationship, on scanning, between the DIP entheses and the nail unit. In PsA, we have seen a correlation between active US changes at the nail and peripheral enthesitis, which requires further analysis. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT03955861.

Background: Biologic drug initiation, follow up and biosimilar switching can be complex but are protocol driven.Clinical commissioning groups (CCGs) mandate six-monthly reviews of biologic treated patients.We have 518 biologic treated patients, which equates to 1,036 clinic appointment per year.We report the successful implementation of a biologics pharmacist to aid in the assessment and follow up of biologic patients in a district general hospital with no rheumatology trainees and limited budget.The aim of the clinic was to provide a pharmacist led biologic clinic to improve patient experience and drug management.Methods: The role developed as an expansion from the holder's role as rheumatology ward pharmacist.A weekly clinic was set up and guidelines for appropriate patient referral from consultant and nurse specialist clinics were made.Eligible patients included biologic naive patients requiring assessment, education and enrolment, stable follow up patients and patients requiring biosimilar switch.The pharmacist ensures funding is approved (via blueteq) and the patient is registered with the relevant homecare company or booked in for their infusion.Training in disease activity assessment was given, and the clinic is situated near an on-going consultant led clinic, though real time support is rarely required.The post is cost neutral as it has been incorporated into an existing job plan.Results: So far 75 patients have been seen in the clinic; 44 RA, 12 AS, 18 PsA and one Behc ¸et's disease.Seeing 36 biologic initiation and 39 biologic follow up patients in total equates to saving an estimated 37.5 hours of consultant or nurse time.95% switch rate to biosimilar versions of infliximab and etanercept patients were achieved.A biologic database capturing key patient information to improve therapy management has been set up and a 30-minute weekly biologic multidisciplinary team meeting has been introduced to discuss complex patients.Capture of patient disease activity scores has been improved to monitor on-going response to therapy.Pre-biologic screening and monitoring requirements following biologic initiation are now clearly documented on clinic letters.Conclusion: Introduction of the specialist biologics clinic has enabled rapid initiation of biologic treatment in the most severely affected patients and assessment of continued response to therapy to satisfy CCG requirements.Enhanced medicines reconciliation and implementation of new audit processes and tools have rationalised the prescribing of biologics.The clinic provides the opportunity for biologic education and gives patients time to voice concerns and queries.It provides an opportunity to enhance pharmacy clinical experience and frees consultant time.Improved structure and realignment of clinical responsibilities have a significant impact on the workforce and patient management.The biologic pharmacist is now the point of contact for biologic drug queries and an essential member of the rheumatology team.

Background/Purpose: Biologic drugs have revolutionised the treatment of Rheumatoid Arthritis (RA), however these therapies are expensive and exhibit a high non–response rate (30%). Currently there are no specific biological markers which distinguish non-response early after initiating treatment. The aim of this study was to identify serum protein levels which change when disease activity score is reduced by biologic drug treatment. These proteins may give mechanistic insight into molecular events after failed therapeutic intervention. Methods: Sera and disease activity scores (DAS28-ESR) were collected from n=25 RA patients at baseline and six months after anti-tumour necrosis factor alpha treatment. EULAR response criteria were used. Untargeted (unbiased) label free LC-MS/MS based proteomics was used initially to discover sera proteins differentially expressed at six months in responders and non-responders. Multiple reaction monitoring (MRM) assays were designed and tested on a triple quadrupole mass spectrometer. Results: Over 500 proteins were identified in each of the pooled serum samples using the untargeted label free LC-MS/MS approach. Statistical analysis of the data revealed a list of 155 proteins that were significantly differentially expressed between good and non-responders (p<0.05). 55 of these proteins were shortlisted for development of targeted MRM assays, and assays were successfully developed for 47 proteins. Conclusion: The approach outlined here and the initial results obtained indicate the power of a combined mass spectrometry strategy for comprehensive serum proteome analysis to determine quantitative changes, discover novel protein signatures and develop a multiplexed protein assay capable of monitoring response to biologic treatments. Such biologic drug response markers could minimise the use of expensive biologic drugs in patients who do not gain benefit and reduce adverse side effects.

OBJECTIVE The main aim of this study was to compare ultrasonography (US) with conventional radiography for the assessment of joint damage in knee OA. METHODS A total of 166 knees of 84 patients (59 women and 25 men) with primary knee OA were included in this study. The femoral hyaline cartilage of the medial para-patellar aspect and the osteophytes of both the medial and lateral femoral condyle were assessed. The cartilage and osteophytes were both quantitatively and qualitatively assessed. The US assessment was feature-specifically compared with conventional radiography. RESULTS There was a strong correlation between the radiographic medial tibiofemoral narrowing grade and the US medial cartilage grade (rs = 0.7144, 95% CI: 0.6218, 0.7873, P < 0.0001). In the detailed analysis, US could assess cartilage damage more correctly by using the direct visualization technique. A strong correlation was also found between the radiographic and the US medial femoral osteophyte grade (rs = 0.7515, 95% CI: 0.6659, 0.8176, P < 0.0001) and between the radiographic and the US lateral femoral osteophyte grade (rs = 0.6947, 95% CI: 0.5941, 0.7739, P < 0.0001). US detected osteophytes in 46 sites at which conventional radiography did not detect any osteophytes. CONCLUSION The present feature-specific comparison study provides evidence supporting the concurrent validity of US in the assessment of knee joint damage due to OA through its agreement with conventional radiography. Moreover, US was found to be a sensitive imaging technique for revealing cartilage damage and even minimal osteophytes, especially in the early radiographic stages of knee OA.

BackgroundPlantar fasciitis is a common cause of heel pain. The aim of this study was twofold: to compare steroid injection with placebo injection and to compare ultrasound guided with unguided steroid injection in the management of this condition.Methods65 patients with inferior heel pain were recruited between November 2008 and June 2011. Heel pain was measured using a visual analogue scale (VAS) at baseline and follow-up 6 and 12 weeks after injection.Results22 patients were randomised to ultrasound guided steroid injection, 21 patients to palpation guided steroid injection and 22 to ultrasound guided placebo injection. There was a significant difference in VAS scores between the groups at 6 and 12 weeks (p=0.018 and p=0.004, respectively). There was a 19.7 (95% CI 2.5 to 37.0) difference in mean VAS scores at 6 weeks between the ultrasound guided steroid group and the placebo group and a 24.0 (95% CI 6.6 to 41.3) difference between the unguided steroid group and the placebo group at 6 weeks. At 12 weeks, the mean difference was 25.1 (95% CI 6.5 to 43.6) and 28.4 (95% CI 11.1 to 45.7) respectively between both steroid injection groups and the placebo group. There was no difference in VAS scores following steroid injection between the ultrasound guided and the unguided groups at either time point. Plantar fascia thickness was significantly reduced after injection in both active treatment groups (p=0.00).ConclusionsIn this study, steroid injection showed a clear benefit over placebo at 6 weeks and this difference was maintained at 12 weeks.Trial Registration NoISRCTN79628180(www.controlled-trials.com).