Seronegative Inflammatory Arthritis Research Articles

Diagnostic Value of Short Course Low-dose Prednisolone in Patients with Clinically Suspected Seronegative Inflammatory Arthritis - A Retrospective Study.

We aim to establish the utility of a trial of low-dose systemic glucocorticoid therapy in the assessment of new clinically suspected inflammatory arthritis patients. We retrospectively identified patients from a private rheumatology practice in Melbourne, Australia between January 1st, 2019, and December 31st, 2021, who presented with clinically suspected inflammatory arthritis and subsequently underwent a trial of low-dose prednisolone (15 mg daily weaned over three weeks in 5 mg increments). We excluded patients with known autoimmune/ inflammatory disorders or concurrent immunosuppression at presentation. We collected basic participant demographic details and clinical details of their presentation, glucocorticoid response, investigations, and treatment. We recruited 177 participants with a median age of 52, and 69.5% were female gender. The median symptom time to presentation was 12 months. Hands were the most affected joint in 63.3% and 85% had bilateral disease. Among the participants, 29.4% had synovitis on clinical review and 75.7% had imaging performed as part of the initial assessment. At presentation, the median CRP was 11 and the median ESR was 16. 79.7% of the cohort experienced significant improvement in their arthritis symptoms from low-dose glucocorticoids and 83.6% of the cohort required long-term immunosuppression for an underlying inflammatory condition. Of those who responded to glucocorticoids, 92.1% were diagnosed with an inflammatory condition. Rheumatoid arthritis was the most common overall diagnosis in 28%. An initial trial of low-dose glucocorticoids in undifferentiated arthritis patients is useful in predicting the diagnosis of inflammatory arthritis. It is also a predictor of further long-term steroid-sparing therapy.

Prevalence of Psoriatic Arthritis among Patients with Arthritis: Insights from a Tertiary Rheumatology Clinic in Bangladesh

Background: Psoriatic Arthritis (PsA) is a complex seronegative inflammatory arthritis associated with psoriasis, characterized by a wide range of clinical manifestations. This study aimed to explore the prevalence of PsA in arthritic patients along with associated demographic and clinical characteristics in a tertiary care setting in Bangladesh. Methods: This cross-sectional study was conducted at the Rheumatology Clinic of Dhaka Medical College Hospital over a period of 6 months from March 2018 to August 2018. A total of 600 arthritis patients underwent screening for PsA, with subsequent evaluations of confirmed cases based on the CASPAR criteria. Demographic and clinical characteristics were documented through face-to-face interviews and physical examination. For data collection, a pre-structured questionnaire was used. Disease activity was assessed using the DAPSA score. The study was conducted according to the ‘Declaration of Helsinki’. The statistical analysis was done with SPSS v-21. Results: The prevalence of PsA in arthritis patients was 5%. Age distribution of PsA showed a majority in between 30-39 years age group with a mean of 36.33±11.86 (SD). Slight female predominance was reported with a percentage of 53.3%. Almost three-fourths of study patients presented with a current diagnosis of psoriasis while the rest had a personal history or family history. A higher incidence (67.7%) of plaque psoriasis was observed followed by sebopsoriasis (20%) and for the rest of the patients, the type of psoriasis was unknown. The disease mostly involved multiple joints (90%), with ankle and metacarpal joints being the most commonly affected at 43.3% and 33.3%, respectively. Disease activity was high in the majority of the patients according to the DAPSA score, representing 53.34% of the patients, with the remainder exhibiting moderate to low disease activity. Conclusion: The study revealed a significant incidence of PsA among the arthritic population which indicates a pressing need for further extensive research on PsA across diverse populations. J MEDICINE 2024; 25: 35-40

Type 17-specific immune pathways are active in early spondyloarthritis

ObjectiveUndifferentiated, early inflammatory arthritis (EIA) can differentiate into seropositive or seronegative rheumatoid arthritis (RA), peripheral spondyloarthritis (SpA) or remain as seronegative undifferentiated inflammatory arthritis (UIA). Little is known about immune...

P30 An unusual infective cause of inflammatory arthritis

P30 An unusual infective cause of inflammatory arthritis

P15 JAKi of all trades

P15 JAKi of all trades

Rice Grain Bursitis: Rare Manifestation of TB in Wrist Joint

This case report highlights about rice grain bursitis- rare manfiestation of TB in wrist joint. Subacromial-subdeltoid bursitis of a shoulder with rice bodies is relatively uncommon. The understanding of the pathogenesis of rice body formation is yet approximate only but some clinical conditions like rheumatoid arthritis, tuberculous arthritis, seronegative inflammatory arthritis, juvenile rheumatoid arthritis and osteoarthritis are related to it. A 30yr Male patient presented with complaints of pain and swelling in the wrist joint , which was insidious in onset. It was associated with evening rise in temperature. Frequenetly erosion of the underlying bone, secondary osteomyelitis and median nerve encasement are present.

Immune-related adverse events after ≥12 months of starting immune checkpoint inhibitors.

e24086 Background: Immune checkpoint inhibitors (ICIs) are well established in the treatment of metastatic renal cell (mRCC) and urothelial carcinomas (mUC). The profile of ICI immune-related adverse events (irAEs) is well described, however, data on timings of toxicity and irAEs occurring at ≥12 months are lacking. Methods: A single-site retrospective audit of mRCC and mUC patients receiving ICI-based therapy for ≥12 months between January 2014 and December 2022. ICI-based therapies included monotherapy and combination therapy with other ICIs or anti-VEGF tyrosine kinase inhibitors (TKIs). Best response to ICI-based therapy and irAEs were described. Results: 199 patients received ICI-based therapy, of which 34% (68/199) received treatment for ≥12 months. Of those on therapy for ≥12 months, 44% (30/68), 25% (17/68), and 31% (21/68) were treated with ICI monotherapy, combination with other ICIs, and TKIs, respectively. At data cut-off, 69% (47/68) were alive. 26% (18/68), 59% (40/68) and 15% (10/68) achieved complete response (CR), partial response (PR) and stable disease (SD), respectively. Overall, 83 irAEs were observed in 74% (50/68) of patients receiving therapy for ≥12 months. Of these, 71% (59/83) occurred at < 12 months and 28% (24/85) at ≥12 months. Corticosteroid therapy was required in 31% (18/59) of irAEs at < 12 months and 63% (15/24) at ≥12 months. Endocrine and cutaneous irAEs mostly occurred at < 12 months, while rheumatic irAEs were more frequently observed at ≥12 months. No ICI-related deaths occurred. At ≥12 months, 71% (17/24) of irAEs were grade 1/2 and 29% (7/24) were grade 3/4. Grade ≥3 irAEs at ≥12 months included colitis (n = 1), proctitis (n = 1), tubulointerstitial nephritis (n = 1), bullous pemphigoid (n = 1) and transaminitis (n = 3). Four patients discontinued treatment, the remainder restarted therapy after irAE resolution. All patients with late-onset grade ≥3 irAEs responded to therapy (CR in 2/7, PR in 5/7). A patient with grade 2 seronegative inflammatory arthritis with onset at ≥12 months also discontinued treatment. Conclusions: Although irAEs are less frequent after 12 months of ICI-based therapy, they remain clinically relevant requiring treatment interruption and discontinuation. Patients require ongoing safety monitoring irrespective of the duration of ICI-based therapy.

OA22 A case report of Whipple's arthritis

Introduction/BackgroundWhipple’s disease is rare chronic systemic infection caused by the Tropheryma whipplei. Initially it was thought it can only affect the Gastrointestinal tract but later on it was discovered that it is multisystemic and can affect heart, brain, skin, eyes and lungs. The common presenting features are gastrointestinal tract symptoms like diarrhoea, vomiting, reduced appetite and weight loss. Other common extra intestinal features are joints pain, uveitis, and confusion and memory loss. Rarely, it can present with seizures and other neurological deficits. It predominantly affects the males as compared to females likely with defective T-Lymphocytes particularly TH1 population function.Description/MethodA 69 year old gentleman presented with unexplained weight loss, chronic diarrhoea, reduced appetite and abdominal bloating with travelling history in the past. Background history of epilepsy, hypercholesterolemia and osteoarthritis. Initial blood tests showed a normocytic anaemia along with lymphopenia. CT thorax and abdomen found indeterminate mesenteric lymphadenopathy. Upper GI endoscopy confirmed tiny proximal stomach tiny polyps, polypectomy was done along with multiple biopsies taken from duodenum. The duodenal biopsies histopathology report had shown an infiltration of PAS stain positive foamy macrophages with mixed inflammatory cells within the lamina propria along with broadening of villi. Furthermore, no micro-organisms were seen, including fungi and mycobacteria along with atypical cells. Histopathology is quite consistent with Whipple's disease however tissue biopsy for Whipple’s PCR was negative but serum Whipple’s PCR was detected. On infectious disease team advice he was started on ceftriaxone for two weeks later, switched to oral trimoxazole for 12 months resulted in complete symptoms resolution along with negative Whipple's PCR.Three months later, Rheumatology team was involved as he had developed palindromic migratory polyarthritis along with raised inflammatory markers, involving his right knee, right wrist, left elbow and then left wrist along with active joint inflammation. Blood investigations had shown weakly positive Rheumatoid factor with negative anti CCP and ANA. The plain films of various joints did not show any early inflammatory changes like periarticular osteopenia and erosions. Infectious disease team had suggested a repeat endoscopy reassuringly, he had negative serum and biopsies Whipple's PCR. After couple of weeks he developed a left knee pain with joint effusion which was aspirated with aseptic technique and the left knee synovial fluid came positive for Whipple’s PCR. On Infectious team recommendation he was commenced on hydroxychloroquine and doxycycline for another 12 months.Discussion/ResultsWhipple’s disease arthritis is easily misdiagnosed and approximately 1.58% of patients with unexplained seronegative inflammatory arthritis are positive for Tropheryma whipplei. Furthermore, the diagnosis of Whipple’s disease can be prolonged in patients with no gastrointestinal tract symptoms and in some cases gastrointestinal symptoms occur after extra intestinal features. In 41%to 61% cases of Whipple’s disease arthritis was reported which indicates Whipple's disease is significantly associated with arthritis and even more in Whipple's prodromal disease where the percentages of joint symptoms peak around 40%-80%. With the antibiotics the outcome of Whipple's disease can be fatal, it can be the worst when patients are misdiagnosed and on immunosuppressants.Giving a reference of retrospective single centre cohort study of seven patients was done. All 7 patients presented with symmetrical polyarthritis and 3 patients developed erosive arthritis. The most common joints were wrists, knuckles and knees involved, less commonly joints involvement were hips, elbows and shoulders. All patients were seronegative and out of 7, 6 patients were given disease modifying agents for considering seronegative rheumatoid arthritis but didn’t get good treatment response. All patients were treated with treated with ceftriaxone along with Co –Trimoxazole or Doxycycline/hydroxychloroquine. Both combinations were used as alternatives due to side effects or inefficacy and eventually lead to arthritis remission over the treatment course of 12 - 27 months. Interestingly, 2 out of 6 patients duodenal biopsies were positive for PAS staining and but all patients synovial fluid from one inflamed joint was positive for Whipple's PCR.The desirable investigations for suspected Whipple's arthritis are for suspected Whipple’s disease are PCR with samples of joint fluid, saliva and stools.In our case, Patient joints symptoms resolved with the course of antibiotics without progression of further joint involvement.Key learning points/ConclusionIn conclusion, Whipple’s disease can rarely present like seronegative arthritis with or without GI symptoms. For patients with seronegative inflammatory arthritis not responding to initial DMARDs therapy, Whipple’s arthritis should be excluded. The positive outcome about Whipple’s arthritis is that it is antimicrobial treatment responsive. In the suspected patients diagnostics test to rule out Whipple's arthritis is minimal invasive synovial fluid tap for Whipple's PCR, which can be performed in routine clinical practice.

P36 Crohn’s-associated inflammatory arthritis treated successfully with upadacitinib

Introduction/BackgroundEnteropathic arthritis is inflammatory arthritis which is associated with inflammatory bowel disease such as Crohn’s disease and ulcerative colitis. The optimal treatment for patients is one which is effective for both arthritis and bowel disease. First line treatments include DMARDs such as methotrexate and sulfasalazine. Second line options include anti-TNF biologics such as infliximab and adalimumab, and the anti-IL-12/23 biologic ustekinumab. There is currently little guidance on choice of treatment if these options fail. We present a case of Crohn’s-associated inflammatory arthritis which did not respond to two anti-TNFs but was successfully treated with the JAK inhibitor upadacinitib.Description/MethodA 30-year-old male was referred to gastroenterology with a 4 month history of diarrhoea and weight loss. His faecal calprotectin was raised at 982µg/g. He had a history of seronegative inflammatory arthritis diagnosed 5 years previously. He had been treated initially with methotrexate and sulfasalazine, which were discontinued due to side effects and inefficacy, and his arthritis was subsequently well-controlled on etanercept for the last year.Colonoscopy showed patchy colitis at the rectum which was continuous in the transverse and ascending colon and caecum. The appearances and mucosal biopsy were consistent with moderately active Crohn’s colitis. In view of this, etanercept was switched to adalimumab, which was administered using the accelerated loading regimen used in IBD.Five weeks after switching the patient developed a flare of arthritis with knee and ankle inflammation and CRP 30. He was given oral steroids and reviewed in a combined rheumatology/gastroenterology clinic. The frequency of adalimumab was increased to 40mg weekly and subcutaneous methotrexate 10mg weekly was introduced.Despite this, the patient’s arthritis remained active, although with some improvement in his bowel symptoms and a fall in faecal calprotectin to 117µg/g. Adalimumab was switched to certolizumab and methotrexate increased to 15mg weekly with intra-muscular steroids. On certolizumab he developed progressively more active arthritis with CRP 83, bilateral ankle inflammation and large knee effusions requiring aspiration and steroid injection.After 8 weeks of certolizumab, there was no improvement and the decision was made to switch to upadacitinib 15mg daily. Within 4 weeks of treatment with upadacitinib he noticed a significant improvement in his arthritis and after 12 weeks was in clinical remission with normal CRP and faecal calprotectin. Methotrexate was later discontinued due to nausea. Over 12 months later the patient remains in remission for both bowel disease and arthritis on upadacitinib monotherapy.Discussion/ResultsIn enteropathic arthritis, joint symptoms may precede or follow bowel disease. Etanercept, a recombinant TNF-receptor fusion protein, is not an effective treatment for IBD. Indeed, there are case reports and observational data to suggest that etanercept may be associated with an increased risk of developing IBD in some patients. In our case the patient developed Crohn’s disease while taking etanercept and the switch to adalimumab precipitated a flare of his arthritis which was not controlled by treatment intensification. The failure of two anti-TNF biologics, adalimumab and certolizumab, may point to the activation of alternative cytokine inflammatory pathways as the driver of the patient’s disease.Our patient was managed in a combined rheumatology/gastroenterology clinic which enabled an inter-specialty approach to managing both aspects of his disease. After the failure of certolizumub we made the decision to trial upadacitinib, a selective JAK1 inhibitor, owing to our experience of its effectiveness in rheumatoid and psoriatic arthritis, and its promising results in Phase 3 trials in Crohn’s disease. We considered ustekinumab but opted against it as in our experience it may be suboptimal in patients in whom arthritis is the most troublesome symptom. Upadacitinib worked quickly and effectively to control our patient’s arthritis alongside his bowel disease and was well tolerated.There are currently limited treatments which are effective for both IBD and arthritis, and there is little guidance on treatment strategies in enteropathic arthritis if anti-TNF and ustekinumab are unsuccessful. Tofacitinib, a JAK1/3 inhibitor, is licensed for rheumatoid and psoriatic arthritis and ulcerative colitis, but is not effective for Crohn’s disease. Upadacitinib is undergoing Phase 3 trials in Crohn’s disease and our case highlights its potential role in the treatment of patients with Crohn’s disease and inflammatory arthritis in whom anti-TNF therapy is unsuccessful.Key learning points/Conclusion1. Etanercept is not an effective treatment for inflammatory bowel disease and may necessitate a change to another anti-TNF biologic such as infliximab or adalimumab.2. Upadacitinib, a selective JAK1 inhibitor, was successfully used in our case to treat both arthritis and bowel disease. Although this was just one case, the results of Phase 3 trials suggest a promising role for upadacitinib in Crohn’s disease and it is already used in the treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.3. Patients with enteropathic arthritis may be best managed in a specialist combined gastroenterology and rheumatology clinic where a holistic approach to the management of both aspects of their disease can be undertaken.

Massive “risotto bursitis” of the great trochanter bursa after proximal femoral varus osteotomy with 5,0 LCP- a case report

The “risotto phenomenon” is a rare pathologic finding, mostly seen as a nonspecific response to chronic inflammation around the shoulder joint- subacromial and subdeltoid bursitis, rheumatoid arthritis, sero-negative inflammatory arthritis, septic arthritis and tuberculous arthritis. A few scientific reports associate rice body formation with the use of different type of osteosynthesis, bony anchors and bioabsorbable sutures. They are usually an incidental asymptomatic finding, requiring no specific treatment, but could be symptomatic demanding surgical excision. We present the clinical case of a 17-year- old female patient with a “risotto bursitis” of the great trochanter bursa, documented during planned surgical removal of a locking compression plate after proximal femoral varus osteotomy for bilateral developmental dysplasia of the hip treatment.

Total hip arthroplasty in ankylosing spondylitis in young patients: A prospective study

Background: Ankylosing spondylitis (AS) is a chronic seronegative inflammatory arthritis of unknown etiology characterized by inflammation of joints of the axial skeleton. It primarily affect the spine and pelvis but peripheral arthritis and enthesitis are common features. The mean age of onset of symptoms is between 15 to 25 years and it is more common in males. Severe disability and functional impairment can result rapidly due to a combination of axial spine and hip involvement. When painful degenerative changes occur, Total Hip Arthroplasty (THA) has been shown to alleviate pain and improve function. The aim of this study is to evaluate the clinical, radiological and functional outcome of uncemented THA in young patients of ankylosing spondylitis.Materials and Methods: This prospective study was carried out in 12 male patients of ankylosing spondylitis all aged above 25 years. Uncemented THA was done in all 12 cases of AS. The study was conducted for a period of 12 months and cases were followed up for a period of 6 months. Functional outcome of hip were evaluated using Harris Hip Score (HHS) at regular intervals.Results: 12 young male AS patients were selected for the study and average age of surgery is 36 years. The final functional outcome of hip on the basis of Harris Hip Score(HHS) were 8(67%) patients good result, 3(25%) patients excellent result and 1(8%) patient have shown fair result. Radiological outcome was passed on the basis of Anterior-posterior (AP) radiograph taken immediate postoperatively and then at 1,2,3,6 months. Radiological outcome was satisfactory except in 3 cases where heterotrophic ossification were noticed in AP radiograph later after 6 months of surgery.Conclusion: This study concludes that uncemented Total Hip Arthroplasty (THA) in young patients done for ankylosing spondylitis provide substantial clinical and functional outcome in patients function. The improvement of in functional outcome and quality of life and postoperative reduction of pain have justified the need of THA in these stiff hips in AS.

Myocarditis and pericarditis following mRNA vaccination in autoimmune inflammatory rheumatic disease patients: A single-center experience.

IntroductionThe mRNA vaccines Comirnaty (Pfizer/BioNTech) and Spikevax (Moderna) are considered safe and highly effective against SARS‐COV2. However, they are also associated with a small increased risk of pericarditis and myocarditis. There is concern about an increased risk of these complications in patients with autoimmune inflammatory rheumatic diseases (AIRD).Case ReportWe describe three patients with pre‐existing AIRD who developed myocarditis or pericarditis shortly after receiving their first dose of the Pfizer‐BioNTech vaccine. The first case is a 31‐year‐old female with systemic lupus erythematosus (SLE) and anti‐phospholipid syndrome (APLS) who presented 7 days after receiving the Pfizer‐BioNTech vaccine and was diagnosed with myopericarditis following a positive troponin and abnormal transthoracic echocardiogram (TTE). The second case is a 29‐year‐old man with seronegative inflammatory arthritis and APLS who presented 7 days after receiving the first dose of the Pfizer‐BioNTech vaccine. His troponin and TTE were unremarkable however his ECG showed widespread ST elevation. Lastly, the third case is a 34‐year‐old man with Behcet's disease with a history of recurrent pericarditis. He developed a recurrence of symptoms approximately 7 days after his Pfizer‐BioNTech vaccine and self‐commenced prednisolone at home. He had normal laboratory and radiological findings. All patients received prednisolone resulting in a quick recovery and resolution of symptoms.DiscussionIn this review we discuss the association between myocarditis, pericarditis and mRNA COVID‐19 vaccines, those who are at greatest risk and current clinical considerations. We also discuss the possible increased risk in AIRD patients and the current research supporting this.

P109 Early diagnosis of inflammatory arthritis (IA) using machine learning analysis of GP referral letters and blood tests to improve pre-hospital referral triage

Abstract Background/Aims The diagnosis of inflammatory arthritis (IA) from referral letters is challenging. We aimed to develop a model integrating GP referral letter data and pre-referral blood test results (BTR) to identify clusters of patient phenotypes (characteristics) that predict at referral that patients will have any of three types of IA (rheumatoid arthritis, seronegative inflammatory arthritis and psoriatic arthritis) requiring early DMARD treatment. Methods The anonymised text of original GP referral letters of patients on our departmental DMARD monitoring database with diagnoses of IA was compared with referral letters of patients with other inflammatory rheumatological conditions (OICs) entered into the same database over the same period. We developed and used novel natural language processing (NLP) methods based on bidirectional encoder representations from transformers (BERT) to identify patients with IA and OICs for triage purposes. Results We have analysed 867 OIC patients and 267 IJD letters using our NLP methods. Data augmentation was used to address imbalance and small data challenges in this real-world application. Our method using only GP referral letters achieved overall accuracy (using confirmed diagnosis as the outcome) of 80% in identifying IJD and OCIs, reaching 86% sensitivity and 84% precision (reproducibility) at detecting OICs, compared with 71% sensitivity and 68% precision in detecting IA patients. Conclusion Our NLP methods alone identified OIC with >80% sensitivity and precision. In data science terms our NLP based method thus has high sensitivity for identifying a wide variety of OICs likely to need DMARD treatment. Our methodology may have great practical value if GP referral letters can be analysed at source. For high specificity and precision very large amounts of data are required to train the NLP model; we had many more OIC letters than IA letters available in analysable formats from other databases in our department. Analysable text of referral letters from primary care is currently difficult to obtain and performing NLP on photographs of referral letters in electronic patient records (EPRs) is a major challenge. These significant bottlenecks in NHS data systems must be removed to allow direct access and analysis of GP referral letters in the compatible format. BTR will be easier to analyse in the EPRs. Combined analysis of pre-referral NLP and BTR may increase the efficiency of automated triage of GP referrals with suspected early IA. Machine learning analysis of GP referrals potentially allows triage of the right patient into the right clinic first time, assisting demand management and capacity in stretched rheumatology clinics and improving patient experience by ensuring the right clinic appointment. Further work is underway to improve the precision of the system with a view to embedding this into our advanced Advice and Guidance triage process. Disclosure A. Bradlow: None. B. Wang: None. W. Li: None. E. Bazuaye: None. A.T.Y. Chan: Member of speakers’ bureau; UCB, Novartis, Sanofi, AbbVie, Celgene and Janssen.

T Helper 2 IL-4/IL-13 Dual Blockade with Dupilumab Is Linked to Some Emergent T Helper 17‒Type Diseases, Including Seronegative Arthritis and Enthesitis/Enthesopathy, but Not to Humoral Autoimmune Diseases

Dupilumab, an IL-4/IL-13 receptor blocker, has been linked to emergent seronegative inflammatory arthritis and psoriasis that form part of the spondyloarthropathy spectrum. We systematically investigated patterns of immune disorders, including predominantly T helper 17‒(spondyloarthropathy pattern) and T helper 2‒mediated disorders and humoral autoimmune pattern diseases, using VigiBase, the World Health Organization's global pharmacovigilance of adverse drug reactions. Several bioinformatics databases and repositories were mined to couple dupilumab-related immunopharmacovigilance with molecular cascades relevant to reported findings. A total of 37,848 dupilumab adverse drug reaction cases were reported, with skin, eye, and musculoskeletal systems most affected. Seronegative arthritis (OR= 9.61), psoriasis (OR= 1.48), enthesitis/enthesopathy (OR= 12.65), and iridocyclitis (OR= 3.77) were highly associated. However, ankylosing spondylitis and inflammatory bowel disease were not conclusively associated. Overall, classic polygenic humoral‒mediated autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus were not associated with dupilumab use. Pathway analysis identified several biological pathways potentially involved in dupilumab‒associated adverse drug reactions, including the fibroblast GF receptor (in particular, FGFR2) pathway. MicroRNAs analysis revealed the potential involvement of hsa-miR-21-5p and hsa-miR-335-5p. In conclusion, IL-4/IL-13 blockers are not unexpectedly protective against humoral autoimmune diseases but dynamically skew immune responses toward some IL-23/IL-17 cytokine pathway‒related diseases. IL-4/13 axis also plays a role in homeostatic tissue repair and we noted evidence for a link with ocular and arterial pathology.

A case report of a severe neonatal systemic vasculitis on the first day of life

BackgroundNeonatal systemic vasculitis syndromes have been reported in infants born to mothers with systemic lupus erythematosus, Sjögren’s syndrome, Behҫet’s disease, cutaneous polyarteritis nodosa and anti-neutrophil cytoplasmic antibody-associated vasculitides. Here we report a novel association of a case of new-onset maternal seronegative inflammatory arthritis associated with a transient systemic vasculitis in a neonate.Case presentationIn the first 24 h of life, a preterm Caucasian baby boy was noted to have blue discoloration to all four extremities. Despite antibiotics, fresh frozen plasma and anticoagulation, the discoloration remained, particularly in the left index finger. This was associated with fever and a maximum C-reactive protein (CRP) of 148 mg/L. Intravenous immunoglobulin (IVIG) was given with short-term improvement. Initial echocardiogram showed enlarged coronary arteries with normalization on repeat 1 week later. Clinical signs and symptoms responded to high dose oral steroid administration. MRI angiography (MRA) of the body and heart showed tortuosity of arteries in the upper and lower extremities with gadolinium uptake, suggestive of vasculitis. Autoantibody profile negative. Genetic panel for hereditary autoinflammatory diseases was negative as was whole exome sequencing performed on the trio. The baby was weaned off steroids by 5 months of age. A small distal autoamputation of the left index finger occurred.He was born to a 28-year-old woman who developed new onset severe symmetrical polyarthritis at 8 weeks gestation. This was presumed a reactive arthritis secondary to a dental infection. Infectious work up and autoantibodies were negative. She was treated with high dose prednisone for the remainder of her pregnancy.The mother was weaned off prednisone, treated with hydroxychloroquine for 8 months post-partum and remains in remission. A repeat MRA done at 1 year old showed mild residual tortuosities of the arteries in the forearms. The remainder of the medium and large vessels were within normal limits with no gadolinium enhancement to suggest active disease. The child is now 4 years old with normal growth and development.ConclusionThis is a unique case of new-onset seronegative presumed reactive arthritis in a mother with the rare development of a successfully treated medium vessel vasculitis in an infant.

O05 A case of cancer mimicking inflammatory arthritis

Abstract Case report - Introduction Rheumatic disease occurring as a paraneoplastic manifestation such as dermatomyositis is well recognised, whilst the symptoms of cancer may frequently mimic the presentations of common rheumatic disorders. It is essential to recognise these differential diagnoses to avoid delay in the detection of malignancy. We present an unusual case of rheumatoid arthritis where, conversely, the diagnosis of inflammatory arthritis was delayed due to the attribution of musculoskeletal symptoms to existing malignancy undergoing treatment. This case highlights the importance of careful history and examination. Cancer and inflammatory disorders may co-exist and delayed diagnosis of either condition can result in increased morbidity. Case report - Case description A 65-year-old male presented to Ear, Nose and Throat (ENT) clinic with a facial lump in association with swelling in his throat, tongue and neck associated with a decrease in appetite and weight loss. He reported an active lifestyle, including mountain climbing until a month prior. He was a non-smoker with alcohol intake of less than 10units/week. Other medical history included osteoarthritis of his left knee which did not limit function. Imaging of the head and neck confirmed a mass in the oropharynx, tonsils, and tongue muscles. Subsequent biopsy revealed moderate to poorly differentiated squamous cell carcinoma (SCC) of the left tonsil. 11 months prior to this presentation, he had developed pain and swelling involving knees, shoulders, and small joints of hands. His mobility became progressively impaired eventually requiring a wheelchair for any outdoor excursion. The systemic and musculoskeletal symptoms were attributed to a paraneoplastic manifestation of his malignant process. A rheumatology opinion was eventually requested in view of the persistence of joint symptoms despite effective cancer treatment with radical radiotherapy. He described early morning stiffness lasting more than 3 hours. Synovitis was evident at his hands, wrists and knees, whilst shoulder movement was restricted, resulting in a high disease activity score (DAS) of 7.44. Blood workup showed normal rheumatoid factor and cyclic citrullinated peptide (CCP). Acute phase markers were elevated with ESR 99 mm/hr, CRP 79 mg/l and ferritin 1194 ng/ml. Ultrasound (US) hands confirmed widespread active synovitis involving bilateral wrist and metacarpophalangeal joints. X-rays showed only degenerative changes. A diagnosis of seronegative inflammatory arthritis was established, and he was initiated on hydroxychloroquine with reducing regime of prednisolone. Methotrexate (MTX) was briefly deferred pending oncology advice. Following initiation of MTX he improved dramatically, returning to normal mobility, and steroids were successfully tapered off. Case report - Discussion Our patient had symptoms of inflammatory arthritis prior to identification of a SCC with local spread; however, his systemic and musculoskeletal features were initially regarded as paraneoplastic. Paraneoplastic arthritides encompass the musculoskeletal manifestations of malignancy. This includes polyarthritis, inflammatory myopathies, hypertrophic osteoarthropathy and palmar fasciitis. Symptoms may precede or occur concurrently with cancer presentations and often respond to treatment of the underlying cancer. Persistence of musculoskeletal symptoms may be a clue to co-existence of a rheumatic diagnosis. Reassessment of history and examination can guide physicians to a concurrent second diagnosis when clinical progress is not as expected. Our case also highlights the question of safe use of immunosuppressive drugs in rheumatic patients with cancer and whether they may promote or induce malignant disease. Literature is challenging to assess as many systemic inflammatory disorders, including RA, have an established increased risk of certain cancers, including lymphoproliferative disease. He was managed by prednisolone and hydroxychloroquine, followed rapidly by MTX, leading to dramatic symptomatic improvement. Low-dose MTX (25—30mg weekly) is considered first-line treatment in RA. Of the commonly used anti-rheumatic therapies it has the least evidence to suggest a potential increased malignancy risk. Other anti -rheumatic drugs such as Tumour Necrosis Factor (TNF) inhibitors also have a favourable risk profile regarding cancer development. Most observational studies evaluating the use of biologic therapy in RA patients with previous solid tumours do not show an increased risk of recurrence. Coordination of care with the patient and their oncologist is essential in the management of cases of individuals with rheumatic disease and concomitant cancer. Case report - Key learning points

O12 A rare mimic of inflammatory arthritis

Case report - IntroductionMelorheostosis is a very rare benign bone disorder involving sclerosing hyperostosis. The name derives from the Greek terms Melos ‘limb’, rheos ‘flow’ and osteon ‘bone’. The incidence of melorheostosis is 0.9 cases per million population, and in the majority of cases is diagnosed before the age of 20 years. It presents with pain, deformities, limitations of a range of motion, contractures, muscle atrophy, and limb swelling. We present a case of a 33-year-old lady who was referred with a history of pain and swelling of the right knee.Case report - Case descriptionThis 33-year-old lady of Nigerian origin was referred to the rheumatology department with a 7-year history of fluctuating pain and swelling in the right knee with the possibility of inflammatory arthritis. Prior to this, she had been seen by the local orthopaedic team with subsequent input sought from the regional specialist orthopaedic bone unit in Birmingham. The synovial biopsies did not show any evidence of inflammation or pigmented villo-nodular synovitis (PVNS). Prior to moving to the UK, she had been assessed in Germany and Dubai due to knee pain and swelling with a diagnosis of the unclear bone-related condition and fibromyalgia. Clinically the right knee had a chronic cool swelling with reduced range of movement but no synovitis and no signs of inflammatory arthritis in other joints. There were no features of seronegative inflammatory arthritis or connective tissue diseases. Investigations showed weak positive ANA with normal CRP, bone profile, FBC, urea and electrolytes, with negative rheumatoid factor and anti-CCP antibody. X-ray knee arranged, showed a flowing periosteal thickening medial cortices of the femur and tibia consistent with ‘melorheostosis’. MRI right knee also confirmed the same diagnosis. Imaging of the upper limbs, spine and pelvis showed no involvement. Input from the metabolic bone health team was arranged who did not deem bisphosphonates useful in her case. Physiotherapy input was arranged to improve her leg posture and movements along with appropriate patient education and analgesia titration.Case report - DiscussionWe present a rare mimic of inflammatory arthritis. Initially referred by GP to orthopaedic team who considered PVNS which was ruled out by biopsies, then next question was about inflammatory arthritis due to recurrent history of knee pain and swelling which is valid differential for monoarthritis. Rheumatology assessment noted a puffy knee but no effusion to aspirate, x-ray imaging was diagnostic for melorheostosis due to the typical presence of ‘dripping wax appearance’. As rheumatologists while assessing joints, genetic and metabolic causes need to be considered besides inflammatory and infective causes. A thorough history remains essential along with interaction with radiology colleagues which is the main learning point. Case report - Key learning pointsNon-inflammatory conditions like melorheostosis can mimic inflammatory arthritisSimple imaging like X-rays and discussion with radiology colleagues are often underrated.

O13 A case of chronic recurrent multifocal osteomyelitis

O13 A case of chronic recurrent multifocal osteomyelitis

POS1195 ASSESSING ANTIBODY STATUS FOR SARS-CoV-2 IN PEOPLE WITH CORONAVIRUS INFECTION: A TIME COURSE STUDY IN PEOPLE WITH AUTOIMMUNE CONDITIONS

Background:With the emergence of the global coronavirus pandemic, increasing concerns have been raised about the course of SARS-CoV-2 infection in people with immune-mediated disorders.Objectives:In this study we aimed to assess the time course of proven SARS-CoV-2 infection, development of humoral immunity with detectable antibodies to the virus and evaluate any changes in antibody titres over time.Methods:We recruited 114 participants in total who had potential symptoms of Covid-19 infection. Participants were recruited from rheumatology or inflammatory bowel disease (IBD) clinics from their records who attended a London Teaching hospital for care. Ethical Approval was in place for the study. Age- and gender- matched control participants without any underlying rheumatological condition/IBD were recruited as a comparator group. Clinical symptoms for Covid-19 infection were assessed using the Covid-19 Rheumatology Global Alliance assessment criteria (https://rheum-covid.org/). Information about Disease Modifying Anti-Rheumatic Drug (DMARD) drug use was also recorded. Participants’ serum samples were collected for quantitative serological assessment of antibodies to SARS-CoV-2 using the Mologic Enzyme-Linked ImmunoSorbent Assay (ELISA) IgG kit. The optical density values were plotted aganist time using a normalisation as previously described (1). A cut-off above 0 indicated positive serology.Results:A total of 114 subjects were recruited into the study. Subjects were recruited if they had suspected Covid symptoms. Of the population recruited, the total number subsequently testing positive for SARS-CoV-2 was n=59 (either on serology or PCR). The number of subjects with autoimmune conditions diagnosed with Covid-19 was 32, with 30 subjects being symptomatic (the asymptomatic 2 subjects were excluded from further analyses). Of the 30 symptomatic subjects, the average age was 56, with a female to male ratio of 19:11. The most prevalent diagnoses were RA (30%), Psoriatic Arthritis (16.7%), SLE (10%), sarcoidosis 10%), Ulcerative Colitis (10%), Crohn’s disease (10%), seronegative inflammatory arthritis (6.7%), Sjogren’s (3.3%) and Juvenile Idiopathic Arthritis (3.3%). The majority were on csDMARDs (60%), biologic DMARDs (20%), tacrolimus (3.3%) and the remaining 16.7% were not on DMARDs. Most subjects required treatment in hospital (56.7%), a smaller number required high dependency care (6.7%) and the rest were treated at home (36.6%). The majority required no oxygen (63.3%), with a further 30% requiring oxygen and 6.7% needed more supportive care i.e. CPAP/ventilation. We also had a matched control group (n=29) of subjects who developed SARS-CoV-2 but had no underlying autoimmune conditions. These subjects had a mean age of 55, female: male ratio 18: 11. Of these 31% had home management, 55.2% had ward level treatments and 13.8% had intensive care treatment. Of the controls, 48.3% did not require oxygen, 37.9% needed simple oxygen and 13.8% were on CPAP. A total of 35 subjects from the original study have attended for follow-up visits. Antibody titres for IgG using the Mologic ELISA detection assay were compared at two visits for the control and autoimmune group. Results showed that subjects with autoimmune conditions and those without who developed SARS-CoV-2 showed very similar antibody titres by optical density (OD) (Figure 1) and maintained antibody responses beyond 6 months in most cases.Conclusion:Serological assays can assist in the understanding of disease severity of SAR-CoV-2 infection. They can be a useful tool for patient surveillance, especially in people who are on immunomodulatory drugs and are being seen in Rheumatology services. Future work is needed to assess the duration and potential protective nature of humoral antibody responses to SARS-CoV-2.

P037 DMARDs & hepatitis E: the hidden culprit

Abstract Background/Aims Disease-modifying anti-rheumatic drugs (DMARDs) require blood monitoring as recommended by the British Society for Rheumatology guidelines. Deranged liver function tests are a common abnormality, and when a significant transaminitis occurs further investigations are required. We wish to present three cases where a transaminitis was caused by acute hepatitis E. Hepatitis E rarely causes illness in the general population. Transmission can occur via sewage-contaminated food and water, undercooked or raw pig and game meat, or processed pork and shellfish. Blood transfusion and solid organ transplantation is very rare. There is an estimated 60,000 cases of Hepatitis E per year in England. Those who are immunosuppressed are more likely to develop chronic liver disease. Methods . Results Case 1 is 55 year old male with a seronegative inflammatory arthritis treated with methotrexate and sulfasalazine whose ALT rose to 2043 U/l. After a negative liver screen including autoantibodies, Hepatitis E IgM was detected. Case 2 is a 71 year old male with seropositive rheumatoid arthritis prescribed Methotrexate and Sulfasalazine who developed a transaminitis following a holiday to Spain. Hepatitis E serology was positive. Case 3 is a 65 year old male with seropositive rheumatoid arthritis on Abatacept and Methotrexate who also developed deranged liver function tests following a trip to Spain. Alcohol excess was initially suspected due to the consumption of > 20 units per week. However, on cessation of all medications the ALT continued to rise to 1087 U/l. He was found to be Hepatitis E IgM positive with viral PCR also detected. In all three cases contaminated food was likely to be the source of infection and DMARDs were successfully restarted in all patients following normalisation of liver function tests. Conclusion This case series highlights an important differential for transaminitis with very little published literature. Hepatitis E is under reported and not routinely requested in practice as part of a liver screen. Failure to check Hepatitis E serology may lead to DMARDs being discontinued inappropriately. All patients should be educated about the risks of Hepatitis E from food products.We recommend that DMARDs are suspended once Hepatitis E infection has been diagnosed in order to allow the immune system combat the infection. Treatment is usually self limiting, though in severe cases Ribavirin has been used with good effect. DMARDs should be restarted once liver markers normalise, and two serum Hepatitis E RNA results and two stool samples are negative. The presence of persistent Hepatitis E RNA (viral shedding) is highly suspicious for chronic infection, which would warrant hepatology input. Disclosure G.A. Brown: None. L. Kearney: None. E. Warner: None. S. Ellis: None.