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O11 Neisseria Meningitidis as a cause of isolated bilateral polyarticular native knee joint septic arthritis

Abstract Case report - Introduction Septic Arthritis is a medical emergency with a significant mortality and morbidity. The aim of management is to minimise the risk of irreversible joint damage and to preserve function. We present the case of a 63-year-old lady admitted with bilateral knee pain and swelling, lower limb rash and a fever who was initially managed as a reactive arthritis but subsequent Polymerase Chain Reaction (PCR) molecular analysis revealed capsular group B N. meningitidis in bilateral knee aspirates. We discuss the diagnostic challenges in differentiating septic arthritis from inflammatory arthritis, and the role of PCR molecular analysis in that process. Case report - Case description A 63-year-old female presented with a 5-day history of painful, stiff and swollen knees bilaterally with decreased range of movement. Five days prior to presentation she suffered from a sore throat, fever and lower limb rash for which she was started on flucloxacillin with some improvement. Co-morbidities included hyperlipidaemia and a hysterectomy. Regular medication included naproxen. On examination her temperature was 37.7C and she was haemodynamically stable. Both knees demonstrated active synovitis. Admission bloods were remarkable for a CRP of 399 and deranged liver function tests. Knee X-rays revealed a moderate effusion in the left knee, and a large effusion in the right. The patient was given a dose of intravenous Co-amoxiclav with a working diagnosis of septic arthritis. Aspiration of both knees was performed with 120 mls of yellow-coloured fluid aspirated from the left knee and 90 mls from the right knee. No organisms were identified on Gram Stain and no growth at 48 hours on culture. Synovial fluid from both knees was sent for broad-based bacterial 16S rDNA PCR molecular testing. The patient was reviewed 4-weeks later at which stage her symptoms had improved. Prednisolone had been stopped a week prior with no deterioration in her joint symptoms. Peripheral blood cultures taken during admission revealed no growth at 5 days. After discharge the results of the molecular PCR testing on the synovial fluid samples became available and were positive for bacterial 16S rDNA. Referral to the Public Health England Meningococcal Reference Unit ensued and further molecular typing confirmed N. meningitidis with capsular genogroup B. Subsequent non-culture sequencing of the factor H binding protein and PorA epitope revealed it to belong to the subtype P 1.12-1,9 and hence the utility of vaccination with Bexsero could not be determined. Case report - Discussion The patient was unusual in having a primary meningococcal arthritis (PMA), defined as an acute septic arthritis without meningitis. The fever and transient rash may have suggested mild meningococcaemia. Direct bacterial invasion of the synovium via the bloodstream is likely to be the route of spread in our patient. Confirming meningococcal disease used to be very challenging with negative peripheral blood culture results confounded by early antibiotic usage and the presence of fastidious and uncultivable organisms. Culture detection of N. meningitidis is 100% specific but is limited by a sensitivity of around 31%. After parenteral antibiotic administration the isolation rate of N. meningitidis drops from 50% to less than 5%. The development of quantitative PCR (qPCR) has improved detection rates and a positive result is diagnostic. qPCR is a culture-independent assay that can quantify bacterial load, is easy to use and has flexibility in design. The broad coverage of qPCR assay is able to use the 16S rRNA gene as a target and hence the overall result of the assay will be able to give both qualitative and quantitative characterisation. The qPCR is a nucleic acid amplification test and hence doesn’t require the presence of viable bacteria for a positive result; and hence the results are not affected by prior antibiotic administration. The sensitivity of PCR has been shown to be higher than blood cultures with values of 47% and 31%, respectively; specificities of PCR have been noted to be above 96%. It has been previously reported that 31% of culture-negative but clinically suspected meningococcal disease cases were subsequently found to be blood PCR-positive. Comparing this with analysis of synovial fluid which has a gram stain sensitivity of between 29% and 50% and a culture sensitivity of up to 76% shows a marked improvement. Case report - Key learning points Our case highlights the challenges in differentiating septic arthritis from a reactive arthritis in a patient presenting with knee pain, swelling and pyrexia who subsequently had N. meningitidis identified via 16S rDNA PCR testing. Emphasis is placed on recognising polyarticular septic arthritis as a clinical entity with early joint aspiration being the priority of care. Polyarticular septic arthritis accounts for an estimated 15% of all cases of septic arthritis with a mean of three affected joints. Mortality rates in monoarticular septic arthritis have been estimated to be around 11%, rising to 50% for polyarticular disease. In our patient the timeline of events is an important factor. It has been reported that patients with septic arthritis typically have symptoms for less than 2 weeks at presentation, with the characteristic features of hot, swollen, painful and restricted joints whereas a reactive arthritis presents 2 to 4 weeks after the preceding infection. Our patient suffered from a sore throat, presumed streptococcal in origin, 5 days prior to her oligoarticular symptoms, which led to admission. It would also be pertinent to consider the relevance of the sore throat 5 days prior to presentation. It has been suggested that a post-streptococcal reactive arthritis is a distinct clinical entity from other forms of reactive arthritis. The peak incidence, age, pattern of joint involvement, extra-articular manifestations and HLA B27 association have been reported to vary between the aforementioned conditions and no causal role has been found for streptococcal throat infection. In conclusion, we have described the first case in the literature of N. meningitidis being identified as the causative organism by PCR assay of synovial fluid in a patient with bilateral septic arthritis of the native knee joint.


1
St George's University, London, United Kingdom, and 2 Pure Sports Medicine, London, United Kingdom Case report -Introduction: High-intensity exercise is effective in treating Axial Spondyloarthritis (SpA). A reduction in morbidity therefore should be gained from accurate diagnosis early in the disease history. In 2021 the National Axial Spondylarthritis Society (NASS) released a statement to reduce time to diagnosis (TTD) of Axial SpA from 8 years to 1, to reduce morbidity and long-term complications of chronic inflammation. This case study aims to provide an example of how a multidisciplinary team working in close clinical proximity (CCP MDT) can be utilised to reduce the TTD and optimise treatment and biomechanics of acute and chronic SpA. Case report -Case description: Cases 1 and 2 compare patients presenting to a musculoskeletal clinic with lower back pain, stiffness, and reduced range of movement. Case 1. Subacute presentation: 25-year-old male with a 3-month history of lower back pain and stiffness. This progressed to a month of not being able to walk, disturbed sleep and morning stiffness of > 1hr. Clinical examination showed no extra musculoskeletal manifestations, and no other joint pain. Tests showed HLA B27 positive status with florid bilateral sacroiliitis on MRI. Case 2. Chronic presentation: 34-year-old male with 20-year history of insidious onset lower back pain previously diagnosed as "nonspecific" back pain by a series of health care professionals (HCPs). HLA B27 negative, MRI showed acute on chronic SIJ arthropathy with juxtarticular sclerosis. Patients were seen by a HCP who referred to a rheumatologist. In both, clinical and radiological signs indicated Axial SpA which was treated with 120mg of IM Depo-Medorone and 8-weeks of strength-based active intervention from a physiotherapist and strength and conditioning coach. BASDAI, 5-rep max single leg press scores were recorded pre-and post-intervention (Table 1.). Case report -Discussion: Conventional therapies for SpA back pain are effective even in chronic cases; this is reflected in the improvements made across both cases. Using a similar approach of high-intensity exercise and mobility both were able to significantly improve BASDAI scores and lower limb strength. We can hypothesise that attempts to innovate the biomechanics of the treatments is missing the fundamental issue surrounding SpA back pain highlighted by NASS; TTD takes too long for too many. There is a feasible argument therefore that it is the structures of how we operate as HCPs that is reducing the efficacy of said treatments. This is evidenced by case 2 (Table 1), whose multiple presentations to different HCPs over 20 years led to potentially preventable prolonged morbidity as well as increased the risk of future complications due to chronic inflammation. This is a story that is sadly reflective of the disease histories of many SpA patients. Much like any primary care provider, patients at this clinic will first present to a HCP. The difference is that all HCPs are trained to recognise features of SpA back pain and encouraged to flag concerns to a doctor. HCPs work in adjacent spaces allowing for better sharing of ideas and concerns that is often reduced by physical separation. This creates the concept of a CCP MDT. HCPs are encouraged to share concerns face to face without reproach or the formality or delay of a written request. This structure has proven to be effective in diagnosis in both of these cases but has proven to be as useful in many more instances to rule out a differential or allay a concern. These cases argue that the low lying fruit of improving clinical outcomes in this cohort is addressing how we as HCPs interact and cooperate. Case report -Key learning points: Biomechanics of the treatments of SpA are effective in the majority of cases when applied by sufficiently skilled practitioners. It is the TTD that we should address to aid the reduction in morbidity in this patient group through the following recommendations: Foster education of SpA in allied health professionals. This allows us to be aware of the boundaries of our own knowledge and at what point a different clinical perspective should be sought. Diversify clinical environments and encourage MDT working. The use of CCP MDT structures allows more nuanced access to different opinions in a safe supportive manner, allowing for sharing of ideas and concerns -allowing for supporting diverse expertise and insight. If we are to reduce TTD to the 1-year NASS hopes for, we should first look at how we work, not what we do. Ongoing research and auditing of patients is being carried out to better assess how educational practices can be optimised to help meet the NASS targets. For more information or to collaborate contact matthew. Case report -Introduction: Septic Arthritis is a medical emergency with a significant mortality and morbidity. The aim of management is to minimise the risk of irreversible joint damage and to preserve function. We present the case of a 63-year-old lady admitted with bilateral knee pain and swelling, lower limb rash and a fever who was initially managed as a reactive arthritis but subsequent Polymerase Chain Reaction (PCR) molecular analysis revealed capsular group B N. meningitidis in bilateral knee aspirates. We discuss the diagnostic challenges in differentiating septic arthritis from inflammatory arthritis, and the role of PCR molecular analysis in that process. Case report -Case description: A 63-year-old female presented with a 5-day history of painful, stiff and swollen knees bilaterally with decreased range of movement. Five days prior to presentation she suffered from a sore throat, fever and lower limb rash for which she was started on flucloxacillin with some improvement. Co-morbidities included hyperlipidaemia and a hysterectomy. Regular medication included naproxen. On examination her temperature was 37.7C and she was haemodynamically stable. Both knees demonstrated active synovitis. Admission bloods were remarkable for a CRP of 399 and deranged liver function tests. Knee X-rays revealed a moderate effusion in the left knee, and a large effusion in the right. The patient was given a dose of intravenous Co-amoxiclav with a working diagnosis of septic arthritis. Aspiration of both knees was performed with 120 mls of yellow-coloured fluid aspirated from the left knee and 90 mls from the right knee. No organisms were identified on Gram Stain and no growth at 48 hours on culture. Synovial fluid from both knees was sent for broad-based bacterial 16S rDNA PCR molecular testing.
The patient was reviewed 4-weeks later at which stage her symptoms had improved. Prednisolone had been stopped a week prior with no deterioration in her joint symptoms. Peripheral blood cultures taken during admission revealed no growth at 5 days. After discharge the results of the molecular PCR testing on the synovial fluid samples became available and were positive for bacterial 16S rDNA. Referral to the Public Health England Meningococcal Reference Unit ensued and further molecular typing confirmed N. meningitidis with capsular genogroup B. Subsequent non-culture sequencing of the factor H binding protein and PorA epitope revealed it to belong to the subtype P 1.12-1,9 and hence the utility of vaccination with Bexsero could not be determined. Case report -Discussion: The patient was unusual in having a primary meningococcal arthritis (PMA), defined as an acute septic arthritis without meningitis. The fever and transient rash may have suggested mild meningococcaemia. Direct bacterial invasion of the synovium via the bloodstream is likely to be the route of spread in our patient. Confirming meningococcal disease used to be very challenging with negative peripheral blood culture results confounded by early antibiotic usage and the presence of fastidious and uncultivable organisms. Culture detection of N. meningitidis is 100% specific but is limited by a sensitivity of around 31%. After parenteral antibiotic administration the isolation rate of N. meningitidis drops from 50% to less than 5%. The development of quantitative PCR (qPCR) has improved detection rates and a positive result is diagnostic. qPCR is a culture-independent assay that can quantify bacterial load, is easy to use and has flexibility in design. The broad coverage of qPCR assay is able to use the 16S rRNA gene as a target and hence the overall result of the assay will be able to give both qualitative and quantitative characterisation. The qPCR is a nucleic acid amplification test and hence doesn't require the presence of viable bacteria for a positive result; and hence the results are not affected by prior antibiotic administration. The sensitivity of PCR has been shown to be higher than blood cultures with values of 47% and 31%, respectively; specificities of PCR have been noted to be above 96%. It has been previously reported that 31% of culture-negative but clinically suspected meningococcal disease cases were subsequently found to be blood PCR-positive. Comparing this with analysis of synovial fluid which has a gram stain sensitivity of between 29% and 50% and a culture sensitivity of up to 76% shows a marked improvement. Case report -Key learning points: Our case highlights the challenges in differentiating septic arthritis from a reactive arthritis in a patient presenting with knee pain, swelling and pyrexia who subsequently had N. meningitidis identified via 16S rDNA PCR testing. Emphasis is placed on recognising polyarticular septic arthritis as a clinical entity with early joint aspiration being the priority of care. Polyarticular septic arthritis accounts for an estimated 15% of all cases of septic arthritis with a mean of three affected joints. Mortality rates in monoarticular septic arthritis have been estimated to be around 11%, rising to 50% for polyarticular disease. In our patient the timeline of events is an important factor. It has been reported that patients with septic arthritis typically have symptoms for less than 2 weeks at presentation, with the characteristic features of hot, swollen, painful and restricted joints whereas a reactive arthritis presents 2 to 4 weeks after the preceding infection. Our patient suffered from a sore throat, presumed streptococcal in origin, 5 days prior to her oligoarticular symptoms, which led to admission. It would also be pertinent to consider the relevance of the sore throat 5 days prior to presentation. It has been suggested that a post-streptococcal reactive arthritis is a distinct clinical entity from other forms of reactive arthritis. The peak incidence, age, pattern of joint involvement, extra-articular manifestations and HLA B27 association have been reported to vary between the aforementioned conditions and no causal role has been found for streptococcal throat infection.
In conclusion, we have described the first case in the literature of N. meningitidis being identified as the causative organism by PCR assay of synovial fluid in a patient with bilateral septic arthritis of the native knee joint.

Hafiz Muhammad Umair and Muhammad Farooq Kazmi Sheffield Teaching Hospitals, Sheffield, United Kingdom
Case report -Introduction: Melorheostosis 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 description: This 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 -Discussion: We 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 points: 1. Non-inflammatory conditions like melorheostosis can mimic inflammatory arthritis 2. Simple imaging like X-rays and discussion with radiology colleagues are often underrated.

ORAL ABSTRACT PRESENTATIONSCHALLENGES IN BONE DISEASE O13 A CASE OF CHRONIC RECURRENT MULTIFOCAL OSTEOMYELITIS
Jessica M Weightman and Geetha L Janakiraman James Cook University Hospital, Middlesbrough, United Kingdom Case report -Introduction: We present the case of a young adult female who presented to rheumatology with persistent arthralgia of her knees despite disease-modifying anti-rheumatic drugs (DMARDs) for seronegative inflammatory arthritis. Her magnetic resonance imaging (MRI) of her knees demonstrated bone lesions compatible with chronic recurrent multifocal osteomyelitis (CRMO). CRMO is a rare autoinflammatory condition of the bone, typically affecting younger female patients. It is characterised by the presence of multifocal inflammatory bone lesions, often affecting the metaphyses of long bones. It can present with localised pain and swelling, and such as in this case, joint swelling.
Case report -Case description: An 18-year-old female patient presented to rheumatology in October 2019 with a 4-week history of left knee monoarthritis. Due to a history of a preceding upper respiratory tract infection, oral non-steroidal anti-inflammatories (NSAIDs) were commenced for possible reactive arthritis. She had no history of seronegative features of psoriasis, uveitis, inflammatory bowel disease, pustulosis or acne. Over the next 4 weeks, she experienced intermittent episodic bilateral knee effusions associated with elevated inflammatory markers. Creactive protein (CRP) peaked at 232mg/L and erythrocyte sediment rate (ESR) at 57mm/1hr. Rheumatoid factor, anti-cyclic citrullinated peptide (CCP) antibodies and antinuclear antibody (ANA) were negative. Plain X-rays of the knees were normal. MRI of the right knee and hip in October 2019 were reported as normal. An ultrasound scan of the i8 https://academic.oup.com/rheumap