President: Dr T Potter Treasurer: Dr H John Secretary: Dr N Erb Dudley Group of Hospitals NHS Foundation Trust Email: [email protected]http://www.midlandrheumatologysociety.org Midland Rheumatology Society Spring Meeting 2020 Friday 20 th March 2020 National Motorcycle Museum Coventry Road, Bickenhill, Solihull, West Midlands, B92 0EJ Hosted by UHCW NHS Trust 08.30 Coffee and Registration 09.00 Welcome and Introduction 09.15 Clinical Papers (Oral Abstracts) 1. Under-reporting of vertebral fragility fractures in CT scans - A missed opportunity for osteoporosis fracture prevention. Byravan S, Comben E, Davda D, Pang W, et al. 2. Does BASDAI Correlate well with Imaging? Review of Leicester Spondyloarthritis service. Jain N, Stairs J, Rennie W J, Moorthy A. 3. The Challenges of Treating Refractory Rheumatoid Arthritis (RA)– The Case for Working with Commissioners to Extend Biologic Options. Hughes K, Barkham N. 4. Anti-neutrophil cytoplasmic antibody (ANCA) positive patients with interstitial lung disease (ILD): A systematic review. Jade J, Chuen Kon F, Ping Kuet K, Kilding R et al. 10.15 CNS Inflammation in Rheumatology Dr Tarunya Arun, Consultant Neurologist, UHCW 11.00 Coffee Break 11.30 All Things Psoriatic Arthritis Dr Laura Coates, Consultant Rheumatologist, Oxford 12.15 Clinical Cases Host Team 13.15 Lunch and Poster Viewing
Transcript
President: Dr T Potter Treasurer: Dr H John
Secretary: Dr N Erb Dudley Group of Hospitals NHS Foundation Trust
There were 105 CT-TAPs performed in patients over the age of 70 years during the audit period (2nd -22nd
Jan 2019): 14 patients were excluded because of bony metastases; 18 of the remaining 91 patients
analysed had moderate/severe vertebral fragility fractures.
Five of the 18 patients had all the vertebral fractures identified in the initial report, 4 patients had
some (but not all levels) of the vertebral fractures reported, and 9 (50%) patients did not have their
fractures reported. None of the scans with vertebral fractures included an appropriate recommendation for
further investigation for osteoporosis.
Out of 18 patients 5 patients had a previous fragility fracture; only one had a recent DEXA scan which
showed low BMD. Only 2 patients were on treatment for osteoporosis, both received bisphosphonates.
There were multiple comorbidities in this cohort of patients including previous cancer in 5 and concurrent
cancer in 9, heart failure, end-stage renal disease and some of them were not appropriate for osteoporosis
treatment.
Conclusion:
Incidental moderate/severe vertebral fragility fractures were identified on CT-TAP in 20% of patients over the age of 70 years in a 3 week period. Only 50% of them were identified on the initial radiology report but none had recommendations for further investigation. This is a missed opportunity for secondary fracture prevention. Increasing awareness of the incidental vertebral fragility fractures in the reporting radiologists and a direct referral pathway to the local fracture liaison service is recommended.
DOES BASDAI CORRELATE WELL WITH IMAGING? REVIEW OF LEICESTER SPONDYLOARTHRITIS SERVICE
Nibha Jain1, Jenna Stairs2, W J Rennie4 , Arumugam Moorthy3
1: Specialist registrar and International fellow, 2: 5th year Medical student, Leicester Medical school, 3: Consultant Rheumatologist & Hon Senior Lecturer, 4: Consultant Radiologist& Hon Reader , University of Leicester & University
Hospitals of Leicester NHS trust, Leicester
Background: The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a commonly used, subjective outcome measurement of disease activity in Ankylosing Spondylitis (AS). BASDAI > 4 is used as a criterion for commencing anti-TNF therapy. Previous studies shown BASDAI correlation with MRI has been proven to be weak. We did this audit to systemically compare clinical and radiological data of patients with AS and to look for the degree of correlation between BASDAI score and MRI changes positive for spondyloarthritis in our cohort of patients.
Methodology: Prospective study of all consecutive patients attending Leicester spondyloarthritis clinic was obtained. Baseline clinical and radiological data was collected after informed consent and anonymizing all patient identifiable information. Microsoft excel and medcalc calculator were used for statistical analysis.
Results: A total of 70 patients were analysed with mean age of 47.2 +/- 11.5 years and having mean BASDAI of 4.2 +/- 2.4. Out of these 40 had MRI scans which could be reviewed to a satisfactory level to determine whether disease is present or not.
Table 1 Active lesions on MRI N=22
No active lesions on MRI N=18
p
Mean BASDAI (SD) 3.98 (2.6) 4.3(1.9) 0.66
Mean ASDAS CRP (SD) 2.14(1.1) 2.04(0.6) 0.73
Mean CRP (SD) mg/l 15.4(22) 17.4(32) 0.8
HLAB27 14 12 0.85
Uveitis 7 7 1
IBP 19 13 0.6
Enthesitis 5 1 0.13
Peripheral Arthritis 3 5 0.27
Dactylitis 0 0 1
Psoriasis 2 2 1
IBD 2 0 0.04
Ethnicity Caucasian Asian
17 5
18 0
0.03 0.03
Age 46.5 (11.2) 46.5(11.3) 1
M:F 14:8 11:7 0.7
Anti TNF therapy 7 0 0.01
BASDAI >4 BASDAI <4
12 12 P=0.43 OR=0.6 10 6
Conclusion Asians had more MRI active disease. There was no statistically significant difference in terms of clinical findings between patients with active MRI disease as compared to inactive disease. The spinal inflammation was similar in patients with AS, irrespective of the corresponding BASDAI level.
References Correlation between clinical and MRI disease activity scores in axial spondyloarthritis:
https://www.ncbi.nlm.nih.gov/pubmed/25894437
Ankylosing spondylitis: correlations between clinical and MRI indices of sacroiliitis activity:
THE CHALLENGES OF TREATING REFRACTORY RHEUMATOID ARTHRITIS (RA) – THE CASE FOR WORKING WITH COMMISSIONERS TO EXTEND BIOLOGIC OPTIONS
Kay Hughes, Nick Barkham. The Rheumatology Department, New Cross Hospital, Wolverhampton
Background: The introduction of the Blueteq funding system in Wolverhampton provided both opportunities and obstacles in prescribing Biologic/Advanced therapies. Blueteq reflected NICE guidelines but as more Biologic options became available it became apparent there were some inequalities in this pathway for new versus existing RA patients. NICE currently approve 3 modes of action of Biologic (in non or loss of response) in RA but 5 are licensed and available. IFRs were the only other option of accessing funding approval but were time consuming to complete and almost always rejected.
Methods: A Business Case was completed with the aim being to improve access to Biologics for all RA patients irrespective of duration of disease and which CCG funds their pharmaceutical care, i.e. to reduce “postcode prescribing” and promote equality, to optimise outcomes for all RA patients and significantly avoid the need for emergency Rheumatology/in-patient care. A 4th or 5th line biologic option would apply if a patient had already had 3 or 4 options and experienced an adverse event or lost response at any time. To provide evidence for the effectiveness of this pathway we performed an audit of the small cohort of patients in Wolverhampton who have received more than 3 lines of biologic use.
Results: At the point of writing the Business case the majority of the 11 patients concerned were on Palliative Rheumatology care often requiring in-patient admission(2-3 per year), phoning the Rheum helpline 2-3 times a week, requiring urgent review appointments (6-8 per year)and numerous oral, IM, IV or IA steroids therapy with very limited effect . Their individual responses to treatment with further biologic/advanced therapies are given in the table. Of the 10 patients who have before and after assessments available 10 (100%) have achieved a response (fall in DAS>1.2) and 5 (50%) achieved remission (DAS 28<2.6). These results are as good as might be expected with earlier lines of therapy.
Conclusions: Multiple biologic refractory RA patients are a difficult group to treat and are not represented in clinical trial populations or in the NICE guidelines. Our audit suggests however that this group of patients can respond to novel therapies and should not be denied access to effective treatments on the basis of long disease duration and prior treatment failure. An effective relationship between Clinicians and Commissioners is essential to enhance biologic therapy options for Rheumatology patients. More Biologic options allow improved outcomes and disease management for our patients, but access to each class of Biologic therapy does not necessarily equate to prescribing every Biologic option.
Results of Audit of >3rd Line Biologic Use In Rheumatoid Arthritis In Wolverhampton Patient no
Age Disease Duration
Sero +ve
MTX Other DMARD
No. Biologics before
Current Biologic Pre DAS 28
Current DAS 28
1 69 1990 Yes No No 5 Baracitinib 7.96 4.5
2 67 2009 Yes No No 5 Baracitinib 8.74 1.89
3 79 1995 No 2.5mg No 5 Tofacitinib 8.27 4.19
4 60 2007 CCP +ve
No Prednisolone 3 Baracitinib 5.89 2.44
5 62 1992 Yes No No 3 Tofacitinib (5mg od) 7.6 4.24
6 71 1982 Yes No Prednisolone 3 Kevzara 8.06 2.33
7 62 1982 Yes 7.5mg No 3 Abatacept 6 2.05
8 77 1980 Yes 2.5mg No 3 Abatacept 6.12 3.36
9 59 2009 RF +ve
25mg No 5 Baracitinib 5.93 4.5
10 49 2009 No 15mg Prednisolone 5 Kevzara 7.83 Aw review
11 62 Transfer Yes 10mg Prednisolone 4 Baracitinib 6.9 2.47
A SERVICE EVALUATION OF THE MUSCLE BIOPSY PATHWAY AT NEW CROSS HOSPITAL Yashaswini Choudhary, Abdus Burahee, Adrian Simons, Pomandeep Dhillon, Nick Barkham
Background: Currently, gold standard for investigation of myositis is a muscle biopsy, as it provides a definitive diagnosis1,2,3. However, muscle biopsy is an invasive procedure which leaves a scar and can give rise to complications such as bruising, bleeding, infection at the site or numbness. At New Cross Hospital (Wolverhampton) muscle biopsies are conducted on site, by the on-call orthopaedic surgeon on the trauma list, and the sample is collected by a technician at the time of surgery and taken to Queen Elizabeth Hospital Birmingham for pathological evaluation. This therefore utilizes theatre time and is potentially costly, on average £1240 (£315 for the day case procedure and £650 - £1600 for the pathology sample). Therefore, it is important to assess whether the current pathway of investigation is effective.
Method: This is a retrospective audit, with data having been collected over a 15-month period and includes all of the 15 patients who underwent muscle biopsy at the request of rheumatology. We collected: patient demographics, indication, site and result of biopsy; blood tests (CK, ANA, ENA and Anti-Jo1) MRI and EMG results.
Results: There were 9 male, 6 female; mean age 58 years (range 33-77). 5 were inpatients (2 of whom were considered ‘medically unfit’) and 10 were out patients. All biopsies were done by an open technique and 14 (93%) were obtained from the quadriceps. There was a significant diagnosis in 12 patients (80%). The most common was ‘statin-induced myopathy’ (4 patients); 2 patients had autoimmune necrotising myopathy; 6 other patients had varying myopathies or myositis. 2 patients had no significant diagnosis and 1 patient did not have a diagnosis established.
All 15 patients had CK results prior to biopsy; 9 patients had CK over 1000. 14 patients were tested for ANA: 6 were ANA positive. 10 were tested for ENA: 3 were ENA positive; no patients were Anti-jo1 positive. Of the 4 patients with statin induced myopathy all (100%) were positive for anti-HMG CoA reductase antibodies.
10 patients (67%) underwent MRI prior to muscle biopsy; 14 (93%) underwent EMG testing. Of those who had MRI, 6 (60%) had a biopsy result which supported the results of the MRI. Of those who had EMG, 9 (64%) had an EMG result which indicated myopathy, and supported the biopsy result.
Discussion: Previous groups have done evaluations of their biopsy pathway2,3, with the major concern being the low frequency of positive diagnosis from muscle biopsy (only 46%)3. Whilst this is a small study, 80% of patients had positive biopsy results indicating that the current use of biopsy is appropriate. This could suggest that improvements have been made selecting patients for biopsy, perhaps due to greater availability of non-invasive testing.
Research has shown that CK>1000 is an important diagnostic factor in myopathies4 and no patient with CK<1000 was diagnosed with an inflammatory myopathy on biopsy but some still had a significant diagnosis. ENA, ANA and Anti-Jo1 were not routinely done and there was little correlation between the results and final diagnosis. The HMGCoA reductase antibodies test however appears to be highly predictive for statin-induced myopathy.
Raised CK levels are a common cause of referral4; traditionally, inflammatory myopathies have been the diagnoses in 2/3 of the positive biopsies done by rheumatology2. Our data set has shown that the commonest cause was statin-induced. This may be due to a change in the epidemiology of myopathy, as there is an increasing population who require lipid lowering therapy.
This data set, while small, has shown that the current pathway being used for muscle biopsy is clinically effective at NXH; it still needs to be considered whether it is cost-effective. As only 2 patients were ‘medically unfit’ it is likely that the biopsies in the majority of cases could be done on an elective operating list.
References 1. Meola G, Bugiardini E, Cardani. Muscle Biopsy. R. J Neurol (2012) 259: 601 2. Chak Hin Szeto M, Wijesooriya S. Audit of muscle biopsy pathway: proof of concept for a local service. Rheumatology (2018) 57;3 3. Cardy CM, Potter T. The predictive value of creatine kinase, EMG and MRI in diagnosing muscle disease. Rheumatology (Oxford) (2007)
46(10):1617-8. 4. Leverenz D, Zaha O, Crofford LJ, Chung CP. Causes of creatine kinase levels greater than 1000 IU/L in patients referred to rheumatology. Clin
ACR50 EFFICACY OF NON-TUMOUR NECROSIS FACTOR BIOLOGICS AND TARGETED SYSTEMIC DISEASE MODIFYING ANTI-RHEUMATIC DRUGS IN THE TREATMENT OF PSORIATIC ARTHRITIS:
A SYSTEMATIC REVIEW AND META-ANALYSIS
Adam Bayley, University of Warwick, Coventry, UK Nicola Gullick, University Hospitals Coventry and Warwickshire, Coventry, UK
Background
Psoriatic arthritis (PsA) is a systemic, inflammatory condition presenting in approximately 30% of patients
with psoriasis and associated with functional impairment and a reduced health-related quality of life. Current
BEWARE DISCORDANT FDG-PET-CT AND TEMPORAL ARTERY BIOPSY RESULTS IN LARGE VESSEL GCA: THREE CASES OF PYREXIA OF UNKNOWN ORIGIN
Arnold W, Bateman J, Adizie T The Royal Wolverhampton NHS Trust
Background The use of FDG PET scanning is becoming more widespread in the investigation of pyrexia of unknown, where rheumatologists are often involved. Methods We report three cases of pyrexia of unknown origin (PUO), where whole-body FDG-PET-CT scans were used successfully and unsuccessfully alongside temporal artery biopsies to demonstrate large vessel vasculitis. Results Case one is a 76-year-old Caucasian male with stable seropositive ACPA positive rheumatoid arthritis on methotrexate monotherapy. He was commenced on prednisolone 15mg in primary care for worsening rheumatoid arthritis symptoms. Weeks later he presented with recurrent fever, general malaise, oral ulceration, and peripheral sensory neuropathy. Steroids were continued. Extensive microbiology, immunology, virology, and imaging tests were unremarkable including CT thorax abdomen and pelvis, MRI whole spine, and Nerve conduction studies. ESR was elevated at 113mm/hr, CRP 283mg/l. A right-sided headache developed without temporal tenderness, bruits or vascular signs. A 17mm temporal artery biopsy was unremarkable. Normal or negative tests included; MRI, MRA, MRV brain; Mantoux test; serial blood cultures, T-spot; and lumbar puncture with cytology and virology. An FDG-PET-CT showed extensive large vessel vasculitis of the aorta, subclavian arteries, and right common carotid. Inflammatory markers and symptoms normalised with IV methylprednisolone and oral corticosteroids, CRP <4, ESR 5 at week 4. Case two is an 82-year-old Caucasian male admitted with a one-week history of fever, night sweats and hypoxia, and raised inflammatory markers (ESR of 132mm/hr, CRP 336), Following treatment for sepsis, he went on to have opinions from infectious disease, urology, microbiology, neurology and haematology. Investigations included unremarkable CT pulmonary angiogram, CT Thorax abdomen and pelvis, MRI whole spine, echocardiogram, lumbar puncture, and extensive microbiology and virology panels. Whole-body FDG-PET-CT showed no evidence of vasculitis, occult sepsis, inflammation, or neoplasm. He had no symptoms of headache, proximal limb-girdle pain or features to suggest PMR. There were no bruits, temporal tenderness, or vascular signs. Symptoms settled with supportive therapy. One month following discharge he presented with unilateral acute visual loss with associated headache to the ophthalmology team, secondary to a central retinal artery occlusion. Temporal artery biopsy showed heavy trans-mural inflammation, disruption of the internal elastic lamina, and multinucleated giant cells, consistent with GCA. Inflammatory markers resolved on appropriate steroid treatment. The third case is that of a 61-year-old Caucasian male with a background of severe atopic eczema and type 2 diabetes, who was admitted with a 6-month history of generalised malaise, 1.5 stone weight loss and intermittent pyrexia, as well as pain and stiffness in the shoulders, wrists, thighs and lower back. During his inpatient admission, he was investigated with CT TAP and trans-oesophageal echocardiograph, neither of which revealed a cause for his symptoms. His immunological results, including rheumatoid factor, anti-CCP, MPO/PR3 antibodies and ANA, all returned negative. Despite the negative findings, he was treated with IV antibiotics and his CRP decreased from 293 to 86. After discharge, he was referred to rheumatology. On examination, he displayed a slightly reduced range of movement in the shoulders and some wrist tenderness, as well as a right subclavian bruit. No other abnormalities were detected and he did not have any temporal artery tenderness. Ultrasound of the temporal and axillary arteries showed widespread chronic intimal thickening more in keeping with atherosclerosis rather than vasculitis. His blood tests returned CRP 175 and Hb 88 with a low MCV, and the patient was subsequently re-admitted. His CT Thorax, Abdomen and Pelvis showed vessel wall thickening of the subclavian vessels. PET-CT scan was arranged, which showed no evidence of malignancy or vasculitis. A temporal artery biopsy was subsequently undertaken, and this showed focal disruption of the elastic layer in the absence of any other classical histological features of GCA. After discussion with a histopathologist, it was concluded that in the context of the clinical features and other
investigations, the findings favoured a diagnosis of arteritis over atherosclerosis. Oral prednisolone 40 mg once daily was commenced and the patient‘s clinical condition improved markedly. Conclusion This case series highlights three important points. Firstly, GCA is an important cause of PUO in elderly patients. Secondly, the diagnosis is frequently elusive and diagnostic tests can show conflicting results – case 3 required 4 different tests to firmly secure the diagnosis. Finally, these cases illustrate the pitfalls in the interpretation of FDG-PETCT and the factors that can result in reduced sensitivity of this investigation.
COMPARATIVE DRUG SURVIVAL OF TNF INHIBITORS AND SECUKINUMAB IN BIOLOGIC NAÏVE PATIENTS WITH ANKYLOSING SPONDYLITIS AND PSORIATIC ARTHRITIS
Myrto Cheila, Karen MJ Douglas, Christos Koutsianas Department of Rheumatology, The Dudley Group NHS Foundation Trust, Dudley, United Kingdom
Background: Secukinumab (SEC) was approved for treating ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in the UK in 2016/17 respectively, providing an alternative mechanism of action to TNF inhibitors (TNFi), which were, until that time, the most frequently prescribed biologic therapies for these rheumatic conditions. SEC’s efficacy and safety has been shown in clinical trials1, 2, but real world data on its survival remains scarce.
Objectives: This study aimed to compare SEC and TNFi drug survival in AS and PsA biologic naïve patients.
Methods: Observational retrospective study of consecutive biologic naïve patients attending the Dudley Group NHS Foundation Trust (DGFT) with a clinical diagnosis of AS (fulfilling ASAS criteria) or PsA (fulfilling CASPAR criteria) who received at least one dose of biologic therapy between 01/07/2017 and 30/09/2019, with a follow-up period until December 31st, 2019 . The biologics database, patient medical records and investigations were reviewed and data on demographics, disease characteristics, previous cDMARD therapy and reasons for discontinuation of biologic were collected. Analysis was performed using descriptive statistics, Kaplan-Meier plots and Cox regression on SPSS version 23.
Results: We identified 153 AS or PsA patients starting biologic therapy in this time interval. 103 (68.7%) were biologic naïve, commencing either TNFi (38, 36.9%), SEC (63, 61.1%) or Ixekizumab (2, 1.9% -excluded from analysis) for AS (45.5%) and PsA (54.5%). The patients were evenly distributed in terms of sex (female 50.5%), had a mean (±SD) age of 45 (±13.8) years and a median (IQR) disease duration of 5 (7.7) years. The median (IQR) follow up time was 13 (13) months.
The overall 1 and 2-year drug survival was 86.8% and 79.3% respectively for TNFi and 81.5% and 77.4% for SEC treated patients. There was no statistically significant difference between the estimated means for drug survival time for the two treatment modalities (TNFi: 24.4 vs SEC:22.9 months, log rank:0.991). The analysis of SEC’s drug survival in AS in comparison to PsA did not show statistically significant difference (21.8 vs 22.0 months respectively, log rank: 0.419). We observed a trend for worse TNFi survival in AS compared to PsA, but this did not reach statistical significance (18.9 vs 26.1 months respectively, log rank: 0.09).
No significant difference in reasons for discontinuation between treatments was observed. Age, sex, disease duration, previous DMARD use and extra-articular manifestations were variables that were not associated with drug survival on Cox regression analysis.
Conclusion: The estimated 1 year drug survival for TNFi and SEC was 86.8% and 81.5% respectively. Data from our cohort of real-life previously biologic naïve patients with AS and PsA showed no difference in drug survival and reasons for discontinuation between TNFi and SEC. Age, sex, previous DMARD use and extra-articular manifestations were not predictors for drug survival.
References: 1. Kavanaugh et al. Secukinumab for Long-Term Treatment of Psoriatic Arthritis: A Two-Year Followup From a Phase
III, Randomized, Double-Blind Placebo-Controlled Study. Arthritis Care Res (Hoboken). 2017 Mar;69(3):347-355. 2. Braun et al. Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results
from the randomised phase III MEASURE 1 study. Ann Rheum Dis. 2017 Jun;76(6):1070-1077
PUBLISH AND BE DAMNED! A CASE OF NEURO-BEHÇET'S DISEASE M Patel, P Chandratre, S Sreekantam, A Sivaguru, J Higham, D Mitton, R D Situnayake
A 38-year-old Asian male doctor who previously published a case report on Neuro-Behçet's disease, developed five aphthous oral ulcers in May 2018. Whilst these ulcers resolved spontaneously, he developed unexplained abdominal pain and had an episode of syncope at work, diagnosed as a vasovagal attack. An abdominal pelvis CT scan was unremarkable. In August 2018, whilst at work, he became acutely confused with significant personality change and mood disturbance. An MRI head scan was normal and following psychiatric assessment, he commenced a combination of Venlafaxine and Mirtazapine. At the age of 20, whilst a medical student, he described a three-month episode of anxiety and mood disturbance with suicidal ideation, with no known triggers, but was not medically assessed. He had no other past medical history. In September 2018, he developed multiple scrotal and penile ulcers, with a negative sexual health screen. These were severe for an eight-week period but slowly resolved. He also developed non-specific visual blurring and a leucocytoclastic vasculitic skin rash on the legs, confirmed on biopsy. He was first seen in the national Behçet's clinic in March 2019, with normal opththalmic and oral assessment and features of resolving vasculitic lesions and scars from genital ulceration. He was diagnosed with probable NeuroBehcets Disease with a Behçet's Disease Clinical Activity Score (BDCAF) of 2/12. His autoimmune and infection screen were negative. Two months later, a recurrence of the vasculitis rash occurred on both legs, which had ulcerated. Despite an
improvement in his mental health, he still had episodes of compulsive buying, becoming easily agitated and angry. An
encephalitis screen was negative. After counselling, he was reluctant to commence immunosuppression at that stage.
In May 2019, his abnormal behaviour and mood disturbance relapsed with paranoid ideation. He was admitted for psychiatry review and discharged with a likely organic cause. This coincided with a relapse of oral and two genital ulcers, together with the reappearance of ulcerated cutaneous vasculitic lesions on his legs. An MRI scan with gadolinium was normal. A lumbar puncture showed evidence of a raised cerebrospinal fluid protein. He received two intravenous pulses of Methylprednisolone at the local hospital. Neuro-Behçet's disease relapse was considered likely. He received a further infusion of IV methylprednisolone and was commenced on a tapering regime of oral prednisolone 30 mg daily, with the plan to start infliximab. In August 2019, prior to going on holiday, he suffered a further recurrence with cutaneous vasculitic lesions on his legs together with restlessness, pacing and mumbling and difficulty with cognition. He was given IV methylprednisolone and his first course of infliximab, which improved his symptoms, but cognitive concerns remained. After his third infliximab infusion and review in October 2019, oral, genital and skin lesions ceased. His mood had improved and he was having fewer episodes of tearfulness with no paranoid ideation. He was started on Azathioprine. In December 2019, his symptoms remained stable. A neuropsychiatric assessment was satisfactory, so he returned to work incrementally. This case highlights the challenge of Neuro-Behçet's diagnosis (1) and the impact of biological therapy in Behçet's disease. Several papers in the psychiatric literature indicate a role for inflammation in depression and psychosis with the concept of ‘immune to brain inflammation’ triggered by an inflammatory process with endothelial and microglial activation. The concurrence of mucocutaneous symptoms, signs of systemic inflammation with psychosis (as seen in our case) indicates a potential role for an inflammatory trigger mediated through an innate response in a susceptible individual (2,3). 1. Uğur Uygunoğlu & Aksel Siva. Behçet’s Syndrome and Nervous System Involvement. Current Neurology and Neuroscience
Reports. 2018; 18: 35. doi:10.1007/s11910-018-0843-5. 2. Golam M. Khandaker & Robert Dantzer. Is there a role for immune-to-brain communication in schizophrenia?
Psychopharmacology (Berl). 2016; 233(9): 1559–1573. doi:10.1007/s00213-015-3975-1. 3. Andrew H. Miller & Charles L. Raison. The role of inflammation in depression: from evolutionary imperative to modern treatment
PANCREATIC CYST: A RARE MANIFESTATION OF GRANULOMATOUS POLYANGITIS
Dr Lauren Dolan, Dr Gen Ho, Dr Asad Khan, Heartlands Hospital, University Hospitals Birmingham
Granulomatosis Polyangiitis (GPA) is a small vessel vasculitis, associated with necrosis and granulomata formation, primarily affecting the upper respiratory tract and kidney vessels. Gastrointestinal involvement is uncommon and pancreatic involvement even more so. We hereby present an unusual manifestation of pancreatic cyst secondary to GPA.
A previously well 23-year-old female, presented generally unwell with fever and weight loss over a 6 week period. Laboratory investigations showed a high inflammatory response with CRP 275mg/L (normal range <5mg/L), and deranged liver function tests of an obstructive pattern. Chest x-ray revealed widespread nodularity and further characterisation with Computed Tomography showed bilateral widespread nodules, mediastinal lymphadenopathy and a suspicious lesion in the pancreas tail. Differential diagnosis included primary pancreatic malignancy or metastatic disease from alternative primary. Subsequent Magnetic Resonance Imaging of the pancreas was not consistent with pancreatic malignancy, describing two well defined cystic lesions instead. A tissue diagnosis was sought; accessible lung nodules revealed acute and chronic inflammatory infiltrate with a granulomatous component and neutrophil micro abscesses but no fibrinoid necrosis, the biopsy was consistent, but not diagnostic of GPA.
Further history revealed symptoms of persistent sinusitis, mouth ulcers, nasal crusting, epistaxis and a persistent dry cough. Immunology showed positive cANCA with PR3 antibodies and infective and viral screen were negative (Tuberculosis, HIV, Hepatitis B and C, legionella serology, respiratory viruses and sexually transmitted disease screen included). Tumour markers for breast, pancreatic, ovarian and bowel cancer were also negative.
A diagnosis of GPA was made; pulsed intravenous methylprednisolone 500mg followed by 1mg/kg oral prednisolone resulted in a good clinical response; assessed by lowering of inflammatory markers and improvement in symptoms.
Following steroids therapy, the pancreatic lesion was investigated with endoscopic ultrasonography (EUS), however no significant mass in the pancreas was visualised and therefore no biopsy was taken.
Management upon discharge included induction with Rituximab, followed by Azathioprine maintenance therapy, a tapering steroid regimen was reduced without relapse. Eighteen months after presentation, Magnetic resonance cholangiopancreatography confirmed reduction in pancreatic tail inflammatory changes with resolution of cystic lesions and only mild residual atrophy; there has been no functional effect on the pancreatic exocrine function.
Our case demonstrates pancreatic involvement of GPA which resolved upon systemic immunosuppressive therapy. Literature review confirms this is a rare manifestation, among reported cases, remission was achieved through immunosuppressive therapy1,2, surgical resection3, or combination of immunosuppressant and surgical treatment4,5,6.
Interestingly two cases of known GPA complicated by pancreatitis and pancreatic cyst development were treated with endoscopic drainage and cauterisation with no increase in immunosuppressive therapy7. It is important to remember that GPA can affect the pancreas in the forms of pancreatic mass, pancreatitis and pancreatic exocrine insufficiency. Given the rarity and lack of evidence, there is currently no consensus regarding the management of pancreatic disease in GPA, management should be tailored to the patient and disease presentation with an emphasis to reduce operative risks where possible.
References 1. Hamilton et al. Delayed presentation of Wegener’s granulomatosis with pancreatic involvement. Int J Rheum dis. 2011;14(4):54-
55 2. O’Neil et al.. Wegeners granulomatosis masquerading as pancreatic carcinoma. Digestive Disease and Sciences.
1992;37(5):702-4 3. Tinazzi I et al. Pancreatic granulomatous necrotizing vasculitis: a case report and review of the literature. Rheumatol Int.
2007;27:989–991 4. Marroun et al. Pancreatic involvement in Wegeners granulomatosis: a rare and difficult diagnosis. Rev Med Interne.
2006;27(2):144-7 5. Christl et al. Pancreatic tail tumor as an unusual first manifestation of Wegeners disease. Gastroenterol. 2004;42(6):513-6. 6. Sahin et al. Two cases of Weheners granulomatosis with pancreatic pseudocyst treated by endoscopic ultrasonography (EUS)-
guided drainage. Turk J Gastroenterol. 2012;23(2):175-180.
IS THIS GOUT? AN INTERESTING CASE OF SWOLLEN MCP JOINTS Dr Mohita Damany and Dr Frances Rees, Nottingham University Hospitals NHS Trust
A 74 year old man, who previously worked as a rare sheep breeder, was referred to Rheumatology with a 1 year history of intermittent swelling of his left hand. His past medical history included gout, renal transplant for reflux nephropathy, CABG and spinal surgery. He was taking Azathioprine 25mg od, Allopurinol 200mg od and Prednisolone 7.5mg od.
He was initially seen by Orthopaedics and trialled with Clarithromycin which settled the swelling. Later, he noticed that the swelling spread from the dorsum of his hand to his MCP joints and had new early morning stiffness. On examination, he had synovitis of his second and third MCP joints. He was rheumatoid factor positive (61.6), anti-CCP negative, had a normal uric acid level and CRP <5. His x-rays and ultrasound showed erosive arthropathy of the left second and third MCP with no evidence of active synovitis. His MCP joints were aspirated and this showed no growth. Clinically, it was felt to be either a seronegative arthritis or chronic gout. Prednisolone 15mg od was trialled with minimal effect.
One month later, he was admitted with painful swollen MCP joints and initially treated for septic arthritis but later felt to be tophaceous gout. Four weeks later, he was reviewed in Rheumatology clinic as there was purulent discharge exuding from the left third MCP joint. 5ml of pus was aspirated and sent for microbiological analysis. He was referred urgently to the hand surgeons for washout and soft tissue samples in the context of severe infection on a background of immunosuppression and no improvement on allopurinol, prednisolone and intermittent courses of antibiotics.
His aspirate revealed acid fast bacilli. He was otherwise asymptomatic and denied any rashes, fever, recent travel, night sweats or weight loss. Examination was otherwise unremarkable. He was referred to the Infectious Diseases team for ongoing treatment. Final cultures demonstrated Mycobacterium Marinum. He was commenced on Ethambutol 900mg OD and clarithromycin 500mg BD. He continued to improve with a reduction in swelling and improved range of motion. His final genome sequencing showed Ethambutol resistance and Rifampicin sensitivity. Due to drug interactions with Azathioprione and his reduced renal function, he was not commenced on Rifampicin or co-trimoxazole. He was consequently treated with Doxycycline 100mg OD (and continued clarithromycin). His CRP was <5. He completed 6 months clarithromycin and 4 months of doxycycline. Two months after treatment he remains stable with no recurrence of his symptoms. Overall, it was felt that the his septic arthritis of his left MCP joints which cultured Mycobacterium Marinum was linked to his previous exposure to sheep due to his occupation of rare sheep breeder.
Learning points:
Mycobacterium Marinum is relatively uncommon. Its natural habitat is aquatic with infection entering via a minor abrasion, laceration or puncture wound.
Importance of history taking- always enquire about previous/current occupation.
Clarithromycin which was initially given had partially treated the infection thus rendering a negative initial aspirate result.
Resistance to single agents ex vivo does not always equate to the same in vivo.
Keeping an open mind to the causes of synovitis and to always have septic arthritis high on the differential list when symptoms are not improving.
AN UNUSUAL CAUSE OF CALF SWELLING IN A PATIENT WITH RHEUMATOID ARTHRITIS
Farhan Javaid, James Francis, Sanaa Fazil Rheumatology Department, Leicester Royal Infirmary (University Hospitals of Leicester NHS Trust)
We present the case of a 73 year old lady with known rheumatoid arthritis(RA) for 15 years, on Sulphasalazine and Methotrexate, who presented with a sudden onset of leg swelling and pain. There was no h/o foreign travel, recent surgery or immobilization and no other risk factors for DVT were found. PMHx: ulcerative colitis, Osteoporosis, Hypertension; she had already developed an unprovoked DVT in the same leg 12 years previously. Thrombophilia screen was negative and patient received anticoagulation for 6 months. O/e : palpable swelling on the postero-medial aspect of the right calf was noted , Rt. calf was erythematous and exquisitely tender to touch ,pulses were intact in RT. Leg and there was no evidence of varicosities. USS scan of leg: showed no ultrasonic evidence of a DVT, but there was superficial soft tissue oedema noted corresponding to the calf swelling. MRI scan of leg: showed large lobulated indeterminate mass of the calf; Sarcoma was raised as a possibility. USS guided Biopsy: Myxoid Liposarcoma. Patient had a CTCAP for staging which showed no evidence of metastases. Treatment: Surgical – the patient had two stage procedure for near-complete resection of the mass in the right calf followed up by the CT guided Radiotherapy to right calf. Outcome: currently under dermatology surveillance for any possible recurrence. Discussion: Myxoid Liposarcoma is a very rare, poorly differentiated tumour (fewer than 2,000 cases per year in UK), accounting for one-half of liposarcomas, with a peak incidence during the fifth decade, 50% metastasis rate and 5 year survival rate between 25% to 90% depended on grading. Cytogenetically, 77% are associated with a chromosomal translocation, t (12; 16) (q13; p11). Myxoid liposarcomas are grossly multinodular, gelatinous masses and microscopically are consist of proliferating lipoblasts in different stages of differentiation. Patients with RA/IBD are at an increased risk of cancer secondary to long-standing inflammation and secondary to immunosuppressive therapies. As the population of patients with RA/IBD ages, there is an increasing risk of cancer development. The use of long term immunosuppression can predispose patients to rare skin, soft tissue and haematological malignancies and tumours. Take home message: Rare soft tissue tumours must be considered in the differential diagnosis of localized limb swellings in patients with autoimmune conditions and immunosuppression.
References:
1.) Weiss, SW., Goldblum, JR. Enzinger and Weiss's Soft Tissue Tumors, Fourth edition, Mosby 2001, 641-690.
2.) Ullman TA, Itzkowitz SH. Intestinal inflammation and cancer. Gastroenterology. 2011;140:1807–1816. [PubMed] [Google Scholar]
We present the case of a 65 year old gentleman worked in a food factory, is an ex-smoker and did not drink alcohol. Was referred by the G.P presented with one year history of painful swollen right hand which was gradually getting worse and he was unable to make a fist. He denied having any other joint problems and there were no symptoms on the left side. Patient is under the respiratory team with diagnosis of TB lymphadenitis after presenting with constitutional symptoms. PMHx: HTN, Diabetes mellitus with poorly controlled disease on insulin, History of cataracts as well as possible mild diabetic nephropathy & retinopathy, O/E: Diffusely swollen right hand with 10 swollen, 10 tender joints including(thumb MCPjs, index, ring and little finger MCPjs & middle PIPj), no joint involvement on left hand side & no other swellings noted. Investigation : CRP09, PV 1.89, FBC, UnE’s , Lft’s ,R.A factor anti CCP & serum ACEi all normal, CXR: left lung upper lobe nodule & mediastinal lymphadenopathy, XR Hand Rt : early degenerative changes, USG Right Hand & wrist: Active synovitis identified to a marked degree involving multiple small joint, Core biopsy right supraclavicular lymph node: Granulomatous inflammation, focally necrotising suggestive of T.B.PET scan: Active lymphadenopathy above and below the diaphragm with fleeting nodules in the lung. Treatment: Taking anti-TB treatment for last 6months. Outcome: Currently under the respiratory Team with a diagnosis of TB lymphadenitis. He is a/w repeat PET scan for monitoring disease activity & currently under rheumatology for any flare up P.D. Discussion: As a result of the recent worldwide resurgence of tuberculosis (TB), extrapulmonary manifestations of TB including arthritis will show an increase as well. Musculoskeletal manifestations are the most common form of extra-pulmonary TB, accounting for 10–19% of the cases. Besides septic TB arthritis, rare examples of non-suppurative reactive arthritis (ReA) have been described in association with TB. This clinical entity became known as Poncet’s disease (PD) is a reactive arthritis due to tuberculous infection elsewhere from the joints. It is a rare aseptic form of arthritis observed in patients with active TB. Resolution of arthritis upon starting of adequate anti-tuberculous therapy is mostly within a few weeks. Conclusion: Presented patient and the review of the literature demonstrate that active TB may be complicated by ReA known as Poncet's disease. Take home message: Early recognition of this rare complication of TB is of major importance to avoid treating it as rheumatoid arthritis with long term immunosuppression also starting appropriate anti-TB treatment early. REFERENCES:
1.Malaviya AN, Kotwal PP. Arthritis associated with tuberculosis. Best Pract Res Clin Rheumatol 2003;17:319–43.
2. Hunfeld KP, Rittmeister M, Wichelhaus TA, Brade V, Enzensberger R. Two cases of chronic arthritis of the forearm due to Mycobacterium tuberculosis. Eur J Clin Microbiol Infect Dis 1998;17:344–8.
PRIMARY VARICELLA ZOSTER VIRUS RESULTING IN DISSEMINATED DISEASE IN A PATIENT WITH GRANULOMATOSIS WITH POLYANGIITIS
Natasha Cleaton FY1, Tom Sheeran Consultant Rheumatologist, Iman Ali Consultant Rheumatologist Background The varicella zoster virus (VZV) has two disease forms. The primary disease, varicella, chicken pox is characterised by a widespread vesicular rash. Following this primary infection VZV enters a latent state within dorsal root ganglia and can be reactivated causing herpes zoster infection. VZV is predominantly an infection of childhood and cases presenting in adulthood tend to have a severe course with associated complications. Granulomatosis with polyangiitis (GPA) is a systemic vasculitis affecting small and medium vessels. The mainstay of treatment for this condition is immunosuppression. Disseminated varicella infection is a rare disease with high mortality in immunocompromised patients. Case A 59-year-old lady with a background of GPA currently managed with rituximab, mycophenolate mofetil, and prednisolone presented with sudden onset epigastric pain, vomiting and fever, with a vesicular rash developing four days into admission. The patient had initially been investigated under the surgical team. Investigations including FBC, U&Es, LFTs and amylase levels had been normal. Blood cultures were negative. Inflammatory markers were raised; the patient continued to be ANCA positive, PR-3 antibody positive. CT thorax abdomen pelvis and abdominal USS were normal. The patient had not responded to IV antibiotics and continued to spike a fever despite antibiotic treatment. Two days into admission the patient was reviewed by rheumatology; immunosuppressive medication was suspended and virology screen carried out. Varicella DNA was detected on polymerase chain reaction (PCR) confirming diagnosis of disseminated VZV. The patient was treated with intravenous aciclovir and made good clinical improvement. Discussion There is an increased risk of VZV infection and greater chance of disseminated infection in immunocompromised patients. In this population presentation may be atypical and delay diagnosis. In our case the patient presented primarily with abdominal pain initially thought to be an acute abdominal problem and was admitted under the surgical team. In immunocompromised hosts the VZV is known to have an unusual presentation with abdominal manifestations such as pain, vomiting and diarrhoea. These features have been known to present several days to weeks before the appearance of the characteristic vesicular rash associated with VZV infection. This sequence of symptoms confuses the diagnosis with the abdominal pain misdiagnosed as an acute abdominal presentation and unwarranted surgical and medical investigations carried out. This has the potential to delay diagnosis and appropriate treatment. In addition, due to the delay in diagnosis the patient had been nursed in a bay rather than a side room exposing other patients to VZV posing an infection control issue and exposed patients had to be contact traced. Another differential was a flare of the patient’s GPA; the typical presenting symptoms of GPA are relatively non-specific including fever, malaise, weight loss and a more typical purpuric rash. Importantly a flare of GPA is managed with further immunosuppression, which would have been fatal in this case of VZV infection. Infection with VZV is usually diagnosed on clinical grounds. However, this can pose a challenge in immunocompromised patients who have atypical presentations. Virology swabs and VZV polymerase chain reaction testing to detect VZV nucleic acids can aid the diagnosis, and were the confirmatory diagnostic tests in our case. VZV infection is treated with aciclovir and should be started promptly in immunocompromised patients. Learning Points Patients with GPA on immunosuppressive medications are at greater risk of primary VZV infection; in these patients the risk of disseminated VZV is increased. GPA patients with disseminated VZV infection may present atypically. There should be a low threshold for considering VZV infections in all GPA patients on immunosuppressive medication, with immunosuppressive medication suspended in VZV infections. If VZV is suspected virology swabs and PCR for VZV nucleic acids should be carried out promptly and aciclovir commenced.
PSORIATIC ONYCHO-PACHYDERMO PERIOSTITIS (POPP): A RARE PRESENTATION OF PSORIATIC ARTHRITIS
Dr J Royle1, Dr A Moorthy2
1. Rheumatology Specialist Registrar, University Hospitals of Leicester NHS trust, UK
2. Consultant Rheumatologist & Honorary Senior Lecturer, University hospitals of Leicester NHS trust Leicester UK
Case report We report an interesting case of an uncommon presentation of seronegative arthritis. A 72-year-old female presented to her General Practitioner with a painful, red and swollen distal phalanx of the left great toe. She was referred to podiatry who pared down the nail but without improvement in her symptoms. A six-week course of flucloxacillin were given without improvement in her symptoms. An MRI was performed in February 2019 which demonstrated oedema/inflammatory changes in the distal soft tissues of the left great toe with marked marrow oedema of the distal phalanx. Osteomyelitis was suspected and a referral to orthopaedics was made. The patient had a further six-week course of antibiotics. She was reviewed by a specialist foot and ankle surgeon who noted the duration of symptoms and lack of response to repeated course of antibiotics. It was felt that the appearance was in keeping with POPP and a repeat MRI obtained. The repeat MRI reported marked thickening of the subungual tissue with surrounding soft tissue oedema of the big toe tuft and intermedullary oedema of the distal phalanx with no erosion. The impression was POPP and not osteomyelitis. Rheumatology referral was made.
In the Rheumatology outpatient clinic, she denied any personal or family history of psoriasis and had no associated seronegative features such as inflammatory eye disease, inflammatory bowel disease or back pain. There was no travel history. She was a retired butcher’s wife but had not been involved in the slaughter of animals. There were no other joint symptoms. Examination demonstrated bilateral 3rd PIPJ and MPCJ tenderness without synovitis. There was no nail pitting but several were markedly ridged. There were no visible areas of psoriasis. The distal left great toe was red, swollen and markedly tender to palpation. The overlying nail appeared grossly normal. Rheumatoid factor and ACPA were negative. Acute phase reactants were normal. The full blood counts and biochemistry were all normal. The patient was started on oral methotrexate 12.5mg once weekly with folic acid co-prescription.
Discussion POPP was recognised in 1989 as an uncommon subset of psoriatic arthritis characterised by psoriatic onychodystrophy, onycholysis, distal digital connective tissue thickening and periosteal reactions1. Treatment is suggested to be similar to psoriatic arthritis and most patient report rapid improvement with low dose methotrexate, however other authors of case reports have suggested leflunomide and anti-TNF therapy2.
Conclusions POPP is a recognised clinical manifestation of Psoriatic arthropathy and treating clinicians need to be aware of this uncommon presentation. Currently there is paucity of literature on management and prognosis. This case also illustrates the importance of foot and ankle examination particularly when suspecting seronegative disease. References 1. Ozbayrak et al. A rapidly progressive variant of psoriatic arthritis: Psoriatic onycho-pachydermo periostitis. Arch
A CASE OF TAKAYASU’S ARTERITIS IN A PATIENT WITH TUBERCULOUS LYMPHADENITIS Tahir Khan, Natasha Cleaton, Tom Sheeran
Royal Wolverhampton NHS Trust Introduction Takayasu’s arteritis (TA) is a large vessel vasculitis that principally affects the aorta and its main branches. The incidence has been reported at between 1.2 – 2.3 cases per million per year, more commonly in the Asian population. The age of onset is typically between tenth and fourth decade; between 80 and 90 percent of the cases are female. The relationship between Mycobacterium Tuberculosis (mTB) and TA has long been considered; both demonstrate chronic inflammatory changes on histological examination and some granuloma formation in arterial walls. There is increasing evidence implicating mTB in the pathogenesis of TA through molecular mimicry between the mycobacterium heat shock protein -65 (mHSP-65) and the human homologue HSP -60 (hHSP-60). However, no definitive link between the two diseases has been explained. Case Presentation A 23-year-old lady was referred to our outpatient rheumatology clinic with a twelve-month history of persistently enlarged cervical lymph nodes on the left side for which she had received six months of anti-Tuberculosis medication. She had been referred to the respiratory physicians who had diagnosed presumed Tuberculous Lymphadenitis, with caseating granulomas demonstrated on biopsy, positive acid-fast bacilli smear but a negative culture. The patient had been initiated six months of anti-Tuberculosis medication; however, her lymphadenopathy showed no improvement. More recently she described a five-month history of weakness, paraesthesia and claudication symptoms in her left upper limb with episodes of dizziness and blurred vision, episodes occurring 2-3 times per day and lasting between a few minutes to a few hours. Her examination at this presentation revealed an unrecordable blood pressure in the left upper limb and 104/67mmHg in the right. There was significant tender lymphadenopathy of the left cervical lymph nodes and diminished pulses in the left upper limb. Right sided pulses were normal. The rest of her examination was normal. Investigations at presentation revealed elevated inflammatory markers with C- reactive protein (CRP) of 116mg/dL and erythrocyte sedimentation rate (ESR) of 128mm/h. Complete blood count (CBC) found her to be anaemic with a haemoglobin of 100g/L, with a mean cell volume of 71.3fl, and have elevated platelet count of 649x 109/L. Recent computerized tomography scan with contrast of the thorax demonstrated features consistent with Takayasu Arteritis. Marked left subclavian stenosis was found on magnetic resonance imaging. High dose prednisolone at 60mg once daily along with Azathioprine 2mg/kg/day was started with a follow up appointment in two weeks. Conclusion There is increasing evidence implicating mTB in the development of TA and a few cases recognising this link have been reported. We report a case of TA in a patient recently diagnosed and treated for Tuberculous lymphadenitis who then developed symptoms of TA. There should be a low threshold for suspecting a diagnosis of Takayasu’s arteritis in patients previously or actively infected with Mycobacterium Tuberculosis. Further research exploring the relationship between mTB and TA is required.
1Department of Rheumatology, Sandwell & West Birmingham NHS Hospitals Trust 2Department of Paediatric Rheumatology, Birmingham Women’s and Children NHS Foundation Trust
Introduction We present a case of juvenile-onset sarcoidosis associated with NOD2 gene mutation. Case history A 17 year old Black British-Caribbean young man presented with polyarthritis at age 3. At diagnosis, he had uveitis and serum ACE was elevated consistent with sarcoidosis. His mother was registered blind reportedly due to chronic uveitis. This prompted the paediatric team to consider familial causes linking ocular and joint involvement; genetic screening showed a NOD2 mutation p.(Arg334Trp).
Discussion Sarcoidosis is a multisystem disorder of unknown cause with non-caseating granulomata as its hallmark feature. Two types of sarcoidosis have been described in children. The more common type is similar to the disease presentation in adults with lung, lymph node and eye involvement in an older child. Early-onset sarcoidosis is rarer, appearing in children under 4 years of age with symmetrical granulomatous boggy arthritis, uveitis and papulo-erythematous rash. Early-onset sarcoidosis carries a worse prognosis and severe complications including blindness, joint destruction and organ involvement may develop. Another type of paediatric granulomatous arthritis is Blau syndrome. This is a condition with identical features to early-onset sarcoidosis but it is distinguished by an autosomal dominant inheritance pattern. Mutations in the NOD2 (nucleotide-binding oligomerization domain containing 2) gene have been implicated in both diseases and have suggested that they are in fact the same disease. The NOD2 gene is located on chromosome 16q12 and encodes a protein Nod2. NOD2 belongs to the NOD-like receptor group of pattern-recognition receptors. It is expressed in cells of the immune system such as neutrophils and macrophages. It is an intracellular receptor that recognises pathogen-associated or damage-associated molecular patterns. Interestingly NOD2 is also expressed in endothelial cells within the choroid and retina. This mutation has also been linked to Crohn’s disease. Most patients develop the classic triad of joint, eye and skin involvement during early childhood. Skin lesions are usually the first feature, appearing as yellowish to brown/red papules. The arthritis is polyarticular involving mainly the wrists, ankles, knees and proximal interphalangeal (PIP) joints. Contractures may develop at the PIP joints leading to camptodactyly. Uveitis may cause photophobia, blurred vision and pain, and risks visual blindness. Paediatric granulomatous arthritis may also cause systemic complications including fever, panniculitis, lymphadenopathy, liver and spleen involvement, salivary gland involvement. Management of paediatric granulomatous arthritis aims to prevent visual complications and joint deformities. Steroids and immune-suppressants, such as methotrexate or azathioprine, are first line management. Learning points Adult rheumatologists need to be aware of familial paediatric granulomatous arthritis and the array of associated complications. This case also demonstrates the relevance of genetic testing for NOD2 mutations where there is suspicion of early-onset sarcoidosis or Blau syndrome. In this patient, suspicion of a familial link was triggered by his mother’s history of visual problems.
AN UNUSUAL CASE OF BEHÇET’S SYNDROME DEVELOPING IN ASSOCIATION WITH POLYCYTHAEMIA RUBRA VERA AND JANUS KINASE 2 MUTATION
Anisha Sekaran1, Priyanka Chandratre1, Jon Higham1, Andrea Richards1, Surendra Karanam1, Sofia Tosounidou1, Sangeetha Baskar1, Sreekanth Sreekantam1, Anton Borg2, Rohan Deva Situnayake1
1Behçet’s National Centre of Excellence, Sandwell and West Birmingham Hospitals NHS Trust,
Birmingham, UK. 2Warwick Hospital, South Warwickshire NHS Trust, Warwick, UK.
Background
Behçet’s syndrome is a rare multi-systemic inflammatory disorder which displays considerable phenotypic
heterogeneity within and across populations during its clinical course. It occurs extremely rarely after the age
of 50. In this report we describe the unusual case of a 58-year-old woman with polycythaemia rubra vera
(PCV) associated with the Janus kinase 2 (JAK2) V617F mutation who subsequently developed Behçet’s.
Case Description
A 58-year-old Caucasian woman with established PCV presented to haematology clinic for routine review.
She reported severe oral and genital ulceration taking up to 3 weeks to heal and was found to have worsening
SENSORY GANGLIONOPATHY AS A POSSIBLE PRESENTING FEATURE OF SJÖGREN’S SYNDROME
Dr Preeya Ummur, Dr Yee Suh Tee, Dr Kirsty Levasseur, Dr Benjamin Fisher University Hospitals Birmingham NHS Foundation Trust
Primary Sjögren’s syndrome is a systemic autoimmune disease affecting the exocrine glands, commonly resulting in dryness of mouth and eyes. It can also rarely present with neurological symptoms most commonly peripheral neuropathies. The case highlights a rare case of sensory and motor neuropathy with some features suggestive of Sjögren’s syndrome as an underlying diagnosis. A 54 year old Caucasian lady was transferred from a local hospital to QEHB for specialist neurology care. She described widespread paraesthesia over two months progressing to lower limb weakness worsening over a two day period. Her symptoms further progressed to involve her arms and new blurred vision. On thorough neurological examination, the positive findings were mild ptosis of the right eye, paraesthesia on palpation of face, upper limbs had a flaccid tone with reduced power and pseudoathetosis on outstretch arms, reduced prioprioception and absent reflexes. Lower limbs were more affected with worse power and absent proprioception. On further questioning she reported previous severe mouth ulcers, possible genital ulcers and painful jaw swelling with long standing history of dry mouth. Schirmer’s test showed normal tear production but saliva production was reduced. MRI brain and spine was reported as pathological enhancement in both optic nerves, no obvious brain parenchymal abnormality, no obvious spinal cord abnormality. Lumbar puncture CSF pro 0.38, white cells 12 (poly 50%, mono 50%), red cells 3700, no organisms on gram stain, opening pressure 21.5 cmH2O. Sural nerve biopsy demonstrated profound loss of sensory axons, severe loss of large myelinated fibres in all fascicles with motor nerve involvement. Muscle biopsy demonstrated chronic neurogenic atrophy. Rheumatology screen showed positive anti Ro 52 antibodies (on an extended myositis screen). EMG demonstrated neurophysiological evidence of widespread marked loss of sensory axons in the upper and lower limbs and partial loss of motor axons in a number of lower limb territories. USS parotid glands showed some possibly mildly abnormal areas, minor salivary gland biopsy was normal. although She received methylprednisolone, IVIG and two courses of plasma exchange. Given some improvement with IV MP/PLEX, they advised starting Mycofenolate mofetil. This case demonstrates a mixed neuropathy picture. Through thorough investigation, many differential diagnoses of mixed neuropathy were considered and excluded (e.g. Guillain Barre, Syphilis, MS, HIV, Hepatitis). Neurological symptoms can develop before the onset of sicca symptoms in Sjogren’s syndrome. With a positive Anti Ro52, xerostomia and clinical improvement with methylprednisolone and plasmaphereses it seems likely there is an underlying autoimmune diagnosis in this case and despite a normal biopsy she would meet the 2016 ACR/EULAR classification criteria for Sjogren’s syndrome.
CASE OF LYMPHOMA IN A PATIENT WITH SYSTEMIC SCLEROSIS
Ganesh Kasavkar, Nicola Gullick University Hospital of Coventry and Warwickshire NHS Trust
Background Systemic sclerosis and haematological malignancies association is well described through case reports and case series data. Lymphoma is a common form of haematological malignancies reported in systemic sclerosis. We present a case of lymphoma in a newly diagnosed case of scleroderma. Case description 51 year old female presented with one year history of joint stiffness and difficulty making a fist to the rheumatology outpatient clinic. Patient was seen at another trust earlier for similar symptoms and was started on methotrexate for inflammatory arthritis. Ultrasound scan on her hands was negative for synovitis. Patient was diagnosed to have dilated cardiomyopathy a year earlier. Clinical examination revealed sclerodactyly and Raynaud’s phenomenon. Patient had positive anti-nuclear antibodies with nucleolar pattern and positive Ro52 antibodies. She complained of exertional dyspnoea and then had lung function tests, which showed early restrictive changes and reduced gas transfer. Further CT scan of chest showed multiple axillary lymph nodes and mammary lymph nodes. Patient gave history of axillary lymph node enlargement five years ago, which was biopsied showed benign picture. Her CT scan was discussed in Breast MDT where plan was made for ultrasound lymph node biopsy. Biopsy findings did not show clear malignancy but pathologists suggested excision biopsy due to suspicious cells. As per MDT discussion she had core lymph node biopsy, which showed Reed-Sternberg cells in keeping with Hodgkin’s lymphoma. Further review by haematologist suggested PET CT, which showed active and enlarged lymph nodes above and below the diaphragm.
Discussion Haematological malignancies associated with systemic sclerosis (SSc) commonly include lymphoma, leukaemia and myeloma. Non-Hodgkin’s Lymphoma constitutes higher number of cases reported in the literature. Hodgkin’s lymphoma is relatively uncommon and in this case two pathologists confirmed it. There are no specific SSc features, which could predict occurrence of haematological malignancy, but occurrence is higher in the first year of SSc diagnosis. Conclusion Lymphadenopathy in connective tissue diseases can be related to malignancy. Systemic sclerosis is associated with haematological malignancies like lymphoma and appropriate investigations should be carried out to rule out the diagnosis.
COLLABORATING WITH PUBLIC HEALTH ENGLAND TO ESTIMATE NATIONAL INCIDENCE OF KAWASAKI DISEASE IN ENGLAND
1Megan Rutter, 1Peter Lanyon, 2Mary Bythell, 2Sarah Stevens, 2Jeanette Aston, 1Fiona A. Pearce, 1Department of Rheumatology, Nottingham University Hospital, 2National Congenital Anomaly and
Rare Disease Registration Service, Public Health England
Background: The true incidence of Kawasaki disease (KD) in England is unknown. In KD treatment with
intravenous immunoglobulin (IVIG) can be life-saving, but it is expensive and in limited supply. In collaboration
with Public Health England’s National Congenital Anomaly and Rare Disease Registration Service
(NCARDRS) we aimed to determine the incidence of KD in England.
Methods: We worked within NCARDRS to access patient-identifiable Hospital Episode Statistics (HES) data,
enabled by their legal permissions. We extracted all patients receiving a primary or additional diagnostic code
for KD between April 2003 - March 2017. For patients identified in Nottingham University Hospitals Trust, we
reviewed the coding accuracy in their medical records. We calculated incidence with 95% Poisson confidence
intervals among children in England using the total number of cases newly diagnosed in the study period.
We used the ONS mid-year estimates for 2016 for the denominator.
Results: 37 patients were coded as having KD in our Trust. All had a clinical diagnosis of KD (positive
predictive value 100%). 32 patients were paediatric cases treated for KD; the remaining 5 patients were
diagnosed in adult life on the basis of angiogram findings. It was not possible to apply classification criteria
because the required information was not always available. During the 13 year study period we identified
3345 cases in children aged <5, and 4234 cases in children <16 in England. The incidence in children aged
<5 years was 7.50 (95% CI: 7.25-7.76)/100,000 person-years, and 40.7% of cases were female. Incidence
in children aged <16 was 3.09 (95% CI: 3.00-3.19)/100,000 person-years, and 41% of cases were female.
Conclusion: Analysis of HES data within NCARDRS has provided population-based estimates of incidence of KD for the whole of England. Our estimates are higher than in previous studies. Validation of coding accuracy has shown our methods were specific. They are likely to be sensitive given KD is always treated in hospital. Accurate incidence estimates are essential for appropriate resource allocation, given the limited availability of IVIG treatment.
Table 1. Annual incidence of Kawasaki disease in children under 5.
1Division of Epidemiology and Public Health, University of Nottingham, 2Department of Rheumatology, Nottingham University Hospitals NHS Trust, 3Department of Rheumatology, Newcastle upon Tyne Hospitals NHS Foundation Trust, 4Department of Rheumatology, Norwich Hospital, 5Department of Nephrology, University Hospitals of Leicester, 6Department of Rheumatology, Ipswich Hospital, 7National Congenital Anomaly and Rare Disease Registration Service, Public Health England.
Background The National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) records those people with congenital anomalies and rare diseases across the whole of England. The NCARDRS Rare Rheumatology Project is establishing methodologies to identify and register people with rare rheumatic diseases. Hospital Episode Statistics (HES), comprising data from all admitted-patient NHS care in England, provides a promising source for case ascertainment. We aimed to confirm the reliability of diagnostic ICD codes for rare autoimmune rheumatic diseases within HES.
Methods We used NCARDRS’ legal permissions (CAG 10-02(d)/2015) to extract cases who had at least one inpatient or daycase admission recorded in HES during 2003 to 2017 with a primary or additional diagnostic code for Kawasaki disease, Takayasu’s arteritis, Adult-onset Still’s disease, Relapsing polychondritis, Polyarteritis nodosa, Granulomatosis with polyangiitis (GPA), Microscopic polyangiitis (MPA) or Eosinophilic granulomatosis with polyangiitis (EGPA). Using Data Sharing Agreements between NCARDRS and NHS Trusts, we reviewed medical records for all cases admitted to one NHS Trust to confirm diagnoses. For ANCA-associated vasculitis (AAV), up to 20 randomly selected cases admitted to 5 Trusts with a diagnostic code of GPA, MPA and EGPA were reviewed.
Results Table 1 shows the positive predictive value (PPV) of each diagnosis at one Trust: Kawasaki disease 100%, Takayasu’s arteritis 91.7%, Adult-onset Still’s disease 42.8%, Relapsing polychondritis 40.0%, and Polyarteritis nodosa 5.0%. For AAV, which had a PPV at the index Trust of 92.0%, the PPV across the 5 Trusts varied from 92.9% to 74.0%. Combining all 5 Trusts PPV for AAV was 85.9%. It was higher in MPA (PPV=98.4%) than in GPA (PPV=83.3%) and EGPA (PPV=77.4)
Conclusion This is the first study to validate the coding of rare rheumatic disease diagnoses within HES data. Our results highlight heterogeneity in coding accuracy both between conditions and between NHS Trusts. Further work is needed to develop and validate algorithms for conditions where HES coding alone has poor positive predictive value, and test sensitivity. National rare disease registration will enable robust, cost-effective and reproducible population-based epidemiology of rare rheumatic diseases across England which is needed to inform service provision and aid development of new treatments.
Table 1: The positive predictive value of codes for AAV in HES
Stephanie R. Harrison1,2, Gurpreet Jutley3, Danyang Li1, Ilfita Sahbudin3, Andrew Filer3, Martin Hewison1,4,
Karim Raza2,3
1Institute of Metabolism and Systems Research, the University of Birmingham, Birmingham, B15 2TT, UK 2Department of Rheumatology, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, B18 7QH, UK
3Institute of Inflammation and Ageing, Research into Inflammatory Arthritis Centre Versus Arthritis and MRC Versus
Arthritis Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham, B15 2TT, UK 4Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, B15 2TT, UK
Introduction: Rheumatoid arthritis (RA) is the commonest chronic inflammatory arthritis associated with extra-articular features. Previous studies have linked RA risk and disease activity with vitamin D-deficiency, but a causal role for vitamin D in RA is still unclear, partly due to heterogeneous study methods and sample populations. Moreover, no studies have focused specifically on vitamin D status (serum levels of 25-hydroxyvitamin D, 25OHD) in early RA and progression from undifferentiated inflammatory arthritis to RA. Objectives: (1) to analyse serum 25OHD in early inflammatory arthritis, (2) to compare 25OHD levels with disease activity and fatigue in early RA and (3) to determine whether low serum 25OHD is associated with progression to RA. Methods: We analysed 791 patients enrolled in the Birmingham Early Arthritis Cohort from 2013-19 at Sandwell and West Birmingham Hospitals NHS Trust and University Hospitals Birmingham NHS Trust. Baseline demographic data, serum 25OHD (ng/ml), and clinical variables including: duration of symptoms, duration of early morning stiffness (EMS), CRP, ESR, anti-CCP antibody status, Rheumatoid factor status, tender and swollen joint counts, DAS28-ESR, DAS28-CRP, Visual Analogue Scale (VAS) pain/fatigue and FACIT scores. Diagnosis was recorded at 0 and 12 months onwards as either RA, psoriatic arthritis (PsA), Undifferentiated Inflammatory Arthritis (UIA), Clinical Suspect Arthralgia (CSA; inflammatory arthralgia without synovitis), or Other. Data were analysed using SPSSv25. Full ethical approval was given for the study (REC12/WM/0258). Results: Baseline demographic data were similar between all groups, with a median symptom duration of 16.8-34.0 days. Baseline 25OHD was not significantly different between groups [median, interquartile range(IQR): RA 46.7, 30.0-73.3; PsA 41.2, 30.0-65.0; UIA 51.4, 30.0-72.3; CSA 47.7, 30.3-73.0; Other 37.0, 24.9-55.3]. In the RA group (n=335), there were no significant differences between 25OHD and measures of disease activity/fatigue (all p>0.150). Finally, we found no association between 25OHD and progression from UIA (n=121) or CSA (n=150) to RA (p=0.554 and p=0.741 respectively). Conclusion: Overall we found no clear association between serum 25OHD and baseline diagnosis, RA disease activity, or progression from UIA/CSA to RA in this large cohort of early RA patients. Limitations of the study include that we were unable to report on levels of vitamin D metabolites other than 25OHD, and were unable to adjust for supplement use/ time of year the sample was taken due to missing data. Future studies into the role of different metabolites of vitamin D in aetiopathogenesis of inflammatory arthritis would provide invaluable insight into the role of vitamin D in inflammatory arthritis better defining the complex role of vitamin D in RA.
AXIAL SPONDYLOARTHRITIS DIAGNOSIS AND MANAGEMENT IN OVER 16s: AN AUDIT OF ADHERENCE TO THE NICE GUIDELINES (2017) AT QUEEN ELIZABETH HOSPITAL
BIRMINGHAM (QEHB) Maiar Elghobashy, Julia Flint and Nicole Amft
Background: Axial spondyloarthritis (SpA) refers to a group of inflammatory seronegative diseases affecting the sacroiliac joints and/or spine, including ankylosing spondylitis and non-radiographic axial SpA(1). The diagnosis can be delayed for up to 10 years due to non-specific presenting features such as back pain, adversely impacting the patient’s long term quality of life(2). The objective of this audit was to assess the management of patients at QEHB according to the NICE guideline “SpA in over 16s: diagnosis and management” (2017)(3), and to identify trends which can be used to improve patient care. Methods: All patients commencing a biologic for SpA from 1/6/2017-12/9/2019 were identified. The patient journey from the point of referral was audited retrospectively. An audit tool based on the NICE criteria was designed, and data extracted from electronic clinical records. BSR (2016) and EULAR (2016) SpA guidelines were also considered. Results: 51 patients (30 male, 21 female) commenced a biologic within the audit timeframe, including 35 commencing their 1st biologic and 16 switching to a new biologic. These patients had been diagnosed from 1989-2019. X-ray was the first imaging investigation in 12 patients: This led to diagnosis in 5, whereas 7 underwent a subsequent MRI. MRI was the initial investigation in 39 patients. Despite showing signs of sacroiliitis on STIR weighted MRI scans, 9/39 patients did not fulfil the ASAS clinical or radiological criteria fully. Trial of 2 NSAIDs prior to starting a biologic was poorly documented (27/51 patients). Biologics used for SpA included adalimumab (1st line n=38, 2nd line n=6, and 3rd line n=1), etanercept (1st n=12 and 2nd n=4), secukinumab (1st n=1 and 2nd n=1) and certolizumab pegol (2nd n=2 and 3rd n=2). 47/51 patients had a BASDAI recorded prior to starting their 1st biologic, but only 18/51 had two BASDAI scores recorded, 4 weeks apart (as per BSR guidelines). 34/51 had a spinal VAS recorded prior to starting (15/51 had two spinal VAS scores recorded 4 weeks apart as per BSR guidelines). Rates for 2nd/3rd line biologics were similar. Response to 1stline biologic treatment was assessed (including BASDAI) ≤12weeks after starting in 22/51. However all patients were assessed within 6 months of starting 1st line or 2nd/3rd line biologics. Following this assessment, 33/51 were continued on their 1st line biologic due to evidence of improvement in their disease, but only 13/33 had a documented fall of >2 points in both BASDAI and Spinal VAS recorded as per guidelines. 2nd line biologics were continued in 8/12 patients assessed to date. With regards to EULAR guidelines, 53% included patients were documented to have been referred to physiotherapy, whereas only 22% were documented to have been given some form of education (e.g. leaflets, support group). Conclusions: This retrospective audit suggests that diagnosis of SpA in this department is predominantly made on MRI scan. This is not in line with NICE guidelines, but in line with local guidance, which takes into consideration the unnecessary radiation exposure of an x-ray in early disease, if it is unlikely to be diagnostic. The documentation of BASDAI and spinal VAS scores could be improved to demonstrate clinical response to biologic drugs in these patients.(2) 1. Proft F, Poddubnyy D. Ankylosing spondylitis and axial spondyloarthritis: recent insights and impact of new classification criteria.
Ther Adv Musculoskelet Dis. 102018. p. 129-39. 2. Danve A, Deodhar A. Axial spondyloarthritis in the USA: diagnostic challenges and missed opportunities. Clin Rheumatol.
2019;38(3):625-34. 3. National Institute for Health and Care Excellence. Spondyloarthritis in over 16s: diagnosis and management (NG65). London:
RHEUMATOLOGY PATIENT PERCEPTION OF CARDIOVASCULAR RISKS: A SURVEY AT A TEACHING HOSPITAL
Nibha Jain1, Anukripa Manivannan2, Aswin Mahesh3, Arumugam Moorthy4 1: Specialist registrar and International fellow,2: Trust grade doctor FY2 Rheumatology,3: Trust grade Foundation year 2,
4:Consultant Rheumatologist & Hon Senior Lecturer, Clinical Academic Tutor, University of Leicester & University Hospitals of Leicester NHS trust, Leicester.
Background: It is well known that individuals with rheumatological conditions are at an increased risk for developing cardiovascular diseases (CVS) and they are the most common cause of mortality. However, there is still lack of awareness about the CVS risk among Rheumatology patients. We carried out a patient survey to assess their awareness and perception of CVS risk associated with their condition. We also assessed if the health professionals attending to these patients gave adequate education to the patients regarding the CVS risk. Methods: This was a prospective cross sectional survey where in multiple-choice questionnaires were distributed to consecutive patients attending rheumatology clinic. The questionnaire contained 18 questions including demographics, diagnosis, medications and their awareness of cardiovascular risks associated with their underlying rheumatic conditions. We also explored as patient attempted any Primary preventive measures for reducing the CVS risk. Results: We collected data of 57 patients with 47% of patients were above 60 years of age with Female: Male ratio of 3:1. Rheumatoid arthritis was the most common diagnosis (60%) with others including AS (22%), SLE(5%). 32% of patients had been suffering from inflammatory disorder for >10 years and 44% believed their disease was still not fully controlled. 37% had family history of heart diseases. More than half of the patients (56%) were unaware of cardiovascular risks associated with their condition and 65% overall reported that they were not personally informed about these risks by the treating health professionals. When we analysed the newly diagnosed patients (<5years) 64% were unaware about the CVS risks which is higher compared to patients with diagnosis of >5 years. We tried to explore any ethnic differences, however the number is too small to compare. We noted that around 60% of white British with rheumatological diagnosis were not aware of CVS risk in our group. When further asked about the primary preventive measures, only 23% engage in exercise, 21% have made diet changes, 12% take aspirin, 16% have quit smoking and only 5% quit alcohol. Conclusion: This was a small pilot study to look at the patient awareness of CVS risks associated with rheumatological conditions. Clearly there is lack of awareness among patients about CVS risks. Furthermore, most of the patients reported they were not educated about the risks from the health professionals. Majority do not engage in any kind of primary preventive measure for heart diseases. It is crucial that the health professionals actively educate patients regarding the CVS risks and the various methods through which these can be prevented. We believe patient-targeted educational programmes and behavioural interventions can be incorporated for holistic patient management. Reference: John, Holly et al. Inflammatory arthritis as a novel risk factor for cardiovascular disease European Journal of Internal Medicine, Volume 23, Issue 7, 575 – 579.
STEROID SPARING AGENTS IN POLYMYALGIA RHEUMATICA: A SYSTEMATIC REVIEW Dr S.Banerjee,Dr K Chaudhuri, Dr A.Desai, Dr N.Gullick
Background: Polymyalgia rheumatica (PMR) is the commonest chronic inflammatory musculoskeletal disease of the elderly, with an age adjusted incidence of 1 per 1000 person-years. The mainstay of treatment for PMR is long term systemic glucocorticoid (GC), which are associated with significant systemic toxicity. There is a need for steroid sparing drugs in PMR to reduce GC cumulative dose and GC induced adverse effects. Objective: To evaluate the role of steroid sparing agents in PMR. Primary outcomes: 1. Steroid sparing effect of the intervention (steroid sparing agent) measured by difference in cumulative
glucocorticoid dose 2. Percentage of patients in remission. Secondary outcomes: 1. Mean reduction of CRP/ESR 2. Adverse event/toxicity the drugs being compared—measured as number of patients with adverse events
in the compared groups 3. Percentage of patients with relapse during study period 4. Mortality Methods: Electronic databases including Medline, Embase and Cochrane databases (CENTRAL) were searched since inception for prospective randomized control trials comparing disease modifying anti rheumatic drugs (DMARDs) and biologics with systemic glucocorticoids in PMR, published in English with more than 20 patients and a minimum study duration of 24 weeks. As different classification criteria for PMR exist, studies were included if they used any accepted classification criteria for PMR. Case series, case reports, retrospective, non-randomized trials, abstracts, systematic reviews and non English language trials were not included. Patients with Giant cell arteritis (GCA) were excluded. Risk of bias and quality was assessed using…. The studies were assessed for cumulative prednisolone dose, proportion of patients in remission, proportion of patients with relapse, reduction in inflammatory markers, adverse events and mortality. Results: 5 studies were selected for final review-- 3 studies involving Methotrexate, one study on azathioprine, one study on Infliximab. The study on Azathioprine had high risk of bias, small sample size and low quality (Level 2 evidence) with high attrition rate but it revealed reduction of daily prednisolone with Azathioprine. A high quality RCT (Level 1) did not confirm a steroid sparing effect with Infliximab vs placebo, and there was no significant difference between relapse or remission rate. Methotrexate studies showed conflicting results: one high quality RCT (Level 1) and one low quality RCT ( Level 2) on Methotrexate revealed statistically significant steroid sparing effect , however the remaining study did not demonstrate between Methotrexate and placebo. Two methotrexate studies assessed the risk of relapse, with conflicting results (relapses 73% placebo vs 47% methotrexate; or no difference). Methotrexate was not associated with increased adverse effects in any of the studies. Azathioprine was associated with significant adverse events resulting in high attrition. A meta analysis was not performed for methotrexate as the studies were heteregenous.
Conclusion: There is a lack of evidence regarding DMARDs and biologics in PMR, with a paucity of high quality RCTs. Methotrexate is an effective steroid sparing agent, and is not associated with increased adverse events. Azathioprine may be effective but is associated with significant adverse events. Infliximab is not an effective steroid sparing agent in PMR. More high quality RCTs are needed to study the efficacy of steroid sparing agents in PMR.
A MULTI-CENTRE AUDIT EVALUATING THE REAL-WORLD EFFECTIVENESS OF SECUKINUMAB IN THE TREATMENT OF ANKYLOSING SPONDYLITIS
Tahir Khan, Natasha Cleaton, Nibha Jain, Girish Kakade, Hem Sapkota, Ramasharan Laxminarayan, Roshan Amarasena, Arumugam Moorthy, Nick Barkham
On the part of the Midlands Ankylosing Spondylitis Collaboration (MASC)
Background Secukinumab is an interleukin–17 inhibitor that has been found to be effective in the treatment of ankylosing spondylitis (AS) in studies, including phase 3 clinical trials, but these are conducted in highly selected patients and it is important to confirm the efficacy and safety in a real world analysis. To be eligible according to NICE guidelines the patient must have demonstrated an inadequate response to conventional therapy, including non-steroidal anti-inflammatory drugs or tumour necrosis factor (TNF) alpha inhibitors. Response to Secukinumab should be assessed after 16-weeks and continued if there has been sufficient response to treatment according to the BASDAI and spinal VAS scores. We conducted a multi-centre audit to assess the response of patients with AS treated with Secukinmab at the 16-week period. Method The data of patients started on Secukinumab for the treatment of their AS from 2017 to 2019 were collected and retrospectively reviewed. Data was collected from four centres including the Royal Wolverhampton NHS trust, Burton NHS Trust, Leicester Royal Infirmary and Robert Jones and Agnes Hunt hospital. Data collected included demographics, previous biologic use, clinical response to treatment, adverse effects; BASDAI, VAS and CRP scores were assessed at initiation of treatment and again at the 16-week time point. Results The data of 92 patients was collected; 4 patients were excluded due to stopping treatment prior to the 16-week mark, due to side effects (2- colitis, 1- uveitis) and patient choice (1). There were 88 patients left for analysis; 67% (59/88) were male, aged between 18-84years (mean 45.9years, Standard Deviation (SD) 14.9). Of the 88 patients 63% (55) had previous use of anti-TNF therapy (40 patients had 1 anti-TNF treatment and 15 had multiple anti-TNF treatment), 37% were anti-TNF naive. Overall, 68% (60/88) of patients showed improvement on clinical assessment at 16-weeks; 77/88 had a recorded BASDAI with an overall group mean reduction of 2.2 (7 (SD 1.7) to 4.8 (SD 2.4)); 75/88 had VAS score documented with a group mean reduction of 3.2 (7.6 (SD 1.6) to 4.4 (SD 2.9); and 55/88 had recorded CRP with an overall group mean reduction of 6.9 (16.6 (SD 24.4) to 9.7 (13.9)).Of the patients with previous anti-TNF use 69% (38/55) demonstrated improvement at 16-weeks on clinical assessment; 46 patients had documented BASDAI scores with a group mean score reduction of 1.8 (7 (SD 1.9) at initiation and 5.2 (SD 2.2) at 16-week); 44/55 had VAS scores documented with reduction in group mean score of 3.1 (7.7 (SD 1.8) to 4.6 (SD 2.8)); 39/55 had a recorded reduction in group mean CRP over the 16-weeks of 5.4 (16.9 (SD 26) to 11.5 (SD 15.8)). Of the anti-TNF naive cohort 76% (25/33) were assessed as having improved at 16-week; 31/33 had documented BASDAI score with a group mean score reduction of 2.8 (7 (SD 1.4) to 4.2 (SD 2.5)); 31/33 had VAS score recorded with a group mean score reduction of 3.2 (7.4 (SD 1.4) to 4.2 (SD 3.1)); CRP was documented in 16/33, mean score reduction of 10 (15.8 (SD 20.8) to 5.3 (SD 5.5)). Side effects were reported in 10% of the total sample including upper respiratory tract infections, colitis, fungal infections, uveitis and lichen planus. Conclusion This multi-centre retrospective analysis found Secukinumab was effective in 68% of patients with AS. Supporting current literature, this study found Secukinumab was effective in both anti-TNF naive and biologic experienced patients and was associated with reduction in BASDAI and VAS scores as well as CRP. These findings support the use of Secukinumab in the treatment of AS, as a first line therapy or for those who have failed anti-TNF therapy. Safety signals observed in the real-word data set were consistent with those seen in the clinical trials and the product label.
CAN A GCA RISK STRATIFICATION SCORE BE HELPFUL IN CLINICAL PRACTICE?
Muhamad Jasim, Priyan Magan, Roaa Awadalla, Richard Brindley, Dave Richards, Alison Hall
James Barraclough, Tochukwu Adizie
Royal Wolverhampton NHS Trust , Wolverhampton, United Kingdom Background: Giant cell arteritis (GCA) is the most common type of large vessel vasculitis. Typically it presents in patients over the age of 50 with a combination of temporal headaches, scalp tenderness, jaw claudication, raised inflammatory markers and visual disturbance. The diagnosis of GCA is often challenging and there is a difficult balance of over and under investigation. There have been several proposed scoring systems to help clinicians risk stratify patients who may present with suspected GCA. One such scoring system, published in 2017, showed clinical utility in a large international multi-centre study. Following analysis by logistic regression on data from 530 biopsies, Ing et al. developed a parsimonious prediction model comprising 5 candidate criteria: age, jaw claudication, ischemia-related loss of visual acuity, platelet count and logCRP (Figure 1). [1]
Objectives: Increasingly, ultrasound doppler imaging is recognised and accepted as satisfactory means of confirming the diagnosis of GCA, with the presence of the halo sign characteristic for GCA. The aim of our study was to determine whether this GCA prediction model accurately predicts positive temporal artery biopsies in a large, real world UK cohort. In addition, we assessed whether this model accurately predicts positive temporal artery ultrasounds. Methods: A retrospective cohort study was performed using electronic medical records of patients referred for temporal artery biopsy (TAB) and temporal artery ultrasound (USTA) for suspected GCA. All TAB performed at the Royal Wolverhampton NHS Trust between June 2014 – June 2018 and all USTA performed between January 2015-January 2019 were analysed. Patients who undergo USTA for suspected GCA at our centre routinely have bilateral temporal and axillary arteries scanned. Patients were excluded if they already had a previous diagnosis of GCA (and the clinical question was suspected flare), or if there was insufficient information available. Results: The total number of patients who underwent a confirmatory diagnostic test (either TAB or USTA) for suspected GCA was 187. Thirteen of these patients met the exclusion criteria, the remaining 174 patients were included for analysis. 126/174 patients underwent a TAB, 63/174 had an USTA. 15/174 had both these were included in the USS cohort because for all these patients the ultrasound was the first diagnostic test performed (Table 1). Our results appear to closely mirror the original multi-centre results with regards to prediction of biopsy positive GCA, with the centiles closely following those in the inception cohort. 0% of the ‘low’ risk probability biopsy cohort were misclassified - none had a positive biopsy. However, 8% of the ‘low’ risk probability ultrasound cohort were misclassified - 2 had a positive ultrasound. Conclusion: Our study, highlights that a probability score for GCA derived from a large multi-centre cohort of patients who were biopsy positive, predicts ultrasound positivity with similar accuracy. Our work reveals that scoring systems are not infallible but can be helpful in guiding clinical decision making References: [1] Ing EB, Lahaie Luna G, Toren A, et al. Multivariable prediction model for suspected giant cell arteritis: development and validation. Clin Ophthalmol. 2017;11:2031–2042. Published 2017 Nov 22.
EVALUATION OF THE GCA SERVICE AT NORTHAMPTON GENERAL HOSPITAL, AND A STUDY OF ROLE OF TOCILIZUMAB IN GCA
Dr P Nandi, Consultant Rheumatologist, Dr A.B Awan SpR Rheumatology, Dr D Ravindran CMT and Dr W KhinNyo CMT, Northampton General Hospital NHS Trust
Introduction Giant cell arteritis (GCA) is one of the commonest vasculitides, with an incidence in the UK of 2.2/10,000 patient years, mainly affecting those >50 years. The over 65 population of Northamptonshire is 117,400 (2014). This equates to around 26 new GCA patients per year in that age group. BSR guidelines recommend urgent specialist referral for patients with suspected GCA. NICE recommends using tocilizumab for maximum of 1 year, in resistant/refractory cases of GCA. Aim The aim was to evaluate the following: 1. Time to see new suspected GCA patients by the Rheumatologist at Northampton General Hospital (NGH) 2. Time to TAB by the vascular surgeon at NGH 3. Reduction in steroid burden by use of tocilizumab Methods Referral letters were examined from the period Jan 2019 to December 2019. Details of the biopsy sample were accessed via the results reporting system. Pre and Post tocilizumab, steroid burden was calculated by reviewing clinic letters. Results There were 70 referrals over the 12 months (50 females: 20 males). Referrals from both ophthalmology and non-ophthalmology took an average of 3.02 weekdays to be seen by Rheumatology. Currently at NGH, a Rheumatologist is only available on weekdays. For the patients who had a temporal artery biopsy, the average time from referral to vascular team to biopsy was 4.5 days. This excludes the biopsies done by the eye team within their department. There were 4 patients on tocilizumab, tocilizumab reduced cumulative steroid dose by 33.58%.
Discussion In various studies tocilizumab has demonstrated an increase in relapse-free survival at 1 year and reduction in the 1 year cumulative glucocorticoid dose. Our data shows that switching to tocilizumab resulted in reducing cumulative dose of steroids by 33.58 percent.
Conclusion The short time from referral to biopsy demonstrates that the service can manage the current number of referrals. This audit provides further evidence of the potential efficacy of TCZ in a particular subgroup of patients with GCA with relapsing/resistant disease.
