OA06 A complex case of thigh pain in Granulomatosis with Polyangiitis (GPA)

Abstract Introduction/Background Rheumatic pain can result from a multitude of aetiologies. We present a complex case of thigh pain as the presenting manifestation of GPA, which required a multi-disciplinary approach to investigate, diagnose and manage. The pain was attributed to lumbosacral plexopathy, a rare neurological manifestation of GPA. The case was further complicated by subsequent leg weakness secondary to steroid-induced myopathy underlining the challenges confronting clinicians in diagnosing and managing complex systemic conditions. Description/Method A 73-year-old male was admitted with severe crampy bilateral thigh and buttock pain associated with reduced exercise tolerance. He had been well, other than a past history of bladder cancer, until 4 weeks previously when he developed a prodrome, sinusitis and epistaxis. Bloods showed raised inflammatory markers, a strongly positive PR3 and a normal CK. On examination he had no synovitis and no vasculitic rash. There was tenderness around the hamstrings and ischial tuberosities. Neurological examination showed no evidence of motor weakness or sensory disturbance. Urine dip showed +1 protein and +1 blood with normal ACR. CT thorax showed no lung involvement. MRI head showed mild mucosal thickening in the ethmoid air cells. Nasal biopsy was inadequate, only showing granulation tissue. MRI spine showed L4/5 central canal narrowing with impingement of traversing bilateral L5 nerve roots. Nerve conduction studies and EMG showed multiple nerves with reduced amplitude on motor and sensory studies, consistent with a bilateral lumbosacral plexopathy. He was treated as systemic GPA with high dose steroids and a plan for rituximab. The patient declined rituximab over Christmas so had methylprednisolone pulses before receiving rituximab. Two weeks later he developed new proximal leg weakness, power 2/5. Repeat MRI spine was unchanged and CK was normal. ANA was weakly positive with a negative myositis blot including Jo-1. MRI thighs showed bilateral symmetrical muscle changes suggestive of acute myositis, intriguingly with onset whilst on high dose steroids. Clinical impression was a steroid myopathy; steroids were weaned and the weakness improved. Eight weeks after rituximab he had significantly improved, with resolution of epistaxis and severe thigh pain and much improved exercise tolerance, as well as inflammatory markers settling and almost normalisation of his PR3 titre. Repeat MRI thighs after a 3-month interval showed a significant reduction in muscle oedema. Discussion/Results The thigh pain was challenging to diagnose. It is anatomically distinct from other peripheral nervous system manifestations reported in GPA, such as distal symmetrical sensory neuropathy (7-10% of GPA), or motor mononeuritis multiplex (2-12% of GPA). However, the pieces fell into place when nerve conduction study confirmed lumbosacral plexopathy. Existing literature suggests that lumbosacral plexopathy typically presents as lower back pain radiating to the leg, often worse in supine position and may be associated with abnormal sensation and weakness in the lower limbs, in keeping with the nature of his thigh pain. Albeit rare, lumbosacral plexopathy has been associated with inflammatory diseases e.g. sarcoidosis, but there is little reporting of lumbosacral plexopathy in GPA specifically. Brachial plexopathy has been reported in microscopic polyangiitis; they proposed that vasculitic arterial ischaemia leads to plexus ischaemia. Wider differentials of plexopathy include diabetic amyotrophy, paraneoplastic phenomenon, autoimmune (including CIDP), localised trauma or infection; these should be ruled out with relevant investigations. His vasculitic ENT symptoms settled with initial high dose steroids, but the excruciating thigh pain did not. When he developed thigh weakness having just received pulsed methylprednisolone, MRI thigh showed changes suggestive of acute myositis, which added another layer of complexity. Normal CK and negative myositis autoantibodies made new-onset myositis unlikely. The multi-specialty consensus was steroid-induced myopathy, which retrospectively seems most plausible as his symptoms improved with steroid reduction, as did interval MRI follow-up scan. MRI, while highly sensitive for detecting muscle disorders, has limited specificity in distinguishing the type of myopathy and therefore is rarely performed in clinical practice to diagnose steroid-induced myopathy. MRI findings must be correlated with the clinical context. If in doubt, a muscle biopsy should be sought. This would form our next line of investigation if his thigh symptoms had not settled. Key learning points/Conclusion The International Association for the Study of Pain (IASP) has recently defined pain as ‘’an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage’’. Acute causes of pain are varied and include local and systemic aetiologies such as inflammatory, infective, traumatic, malignant and iatrogenic. At presentation, the patient’s main symptom was “excruciating severe cramping pain”. This case emphasizes the importance of a thorough clinical approach comprising detailed history and examination which guided focussed investigations and discussions with specialised multi-disciplinary teams (rheumatology, ENT, radiology, neurology, neurophysiology) to unravel the complexity of this clinical scenario. Whilst peripheral nervous system involvement, most frequently mononeuritis multiplex, is common in ANCA-associated vasculitis, plexopathy is not; however, discussion with the neurophysiologist was extremely helpful in interpreting complex neurophysiology tests to appreciate it was a vasculitic manifestation. As symptoms evolve, always consider if they reflect the underlying disease or are sequelae of treatment. The likelihood of developing acute myositis whilst on high dose steroids was less plausible than a steroid myopathy; always treat the patient and the clinical scenario. Interval scanning can be helpful to monitor progress and response to treatment; in this case it was reassuring that repeat MRI thigh showed a reduction in muscle oedema once steroids were decreased. Whilst “common things are common”, rare presentations of rare conditions also occur; utilise the expertise of your MDT in these situations.

on repeat testing since. Therefore, it is probable that this patient has primary APS as opposed to secondary APS in association with SLE. However, it is possible that this patient may develop more symptoms of SLE over time. When this patient presented with foot rash there were high numbers of children presenting with varying severity of painful, itchy toes coined 'covid toes' due to suspected link to SARS-CoV-2 infection. Patient had exposure history, and COVID antibody serology was difficult to interpret due to recent vaccination. Dermatology found appearance to be consistent with 'covid toes' and advised supportive treatment. The triple APS antibody positivity result provided probable aetiology. Providing evidence of thrombus was problematic with false reassurance from apparently normal lower limb arterial doppler when actually popliteal arteries were not checked in view of the presence of normal flow proximally at the groin and distally in the feet. This case highlights the need to continue to search for thrombus in presence of high titres antiphospholipid antibodies and particularly in the case of triple positivity as although patient presented with colour change to toes, she was entirely asymptomatic from her PE and her left foot improved spontaneously despite a left popliteal thrombus also being present. Key learning points/Conclusion: Non-criteria manifestation of thrombocytopenia (occurs in 25% paediatric APS patients) was present throughout and patient had past history of haematuria (a recognised renal non-criteria manifestation). A paediatric specific APS criteria including these may have resulted in earlier detection of triple antiphospholipid antibody positivity and thus earlier treatment escalation and possible avoidance of thrombus. It has been reported that a high proportion of children with positive antiphospholipid antibodies don't develop a thrombus. However, it is interesting that our patient was entirely asymptomatic from her pulmonary embolus which was an incidental finding on her CT angiogram. This prompts a discussion about how much imaging should be performed in those with high levels of persistent positive antiphospholipid antibodies. Rituximab resulted in normalisation of platelet count and ESR for the first time since initial presentation. Anticardiolipin antibodies normalised, lupus anticoagulant decreased from strong to moderate and anti-B2 glycoprotein levels decreased but remained positive. Rituximab is a recognised treatment for catastrophic antiphospholipid syndrome (CAPS) but not routinely used in APS. The consistently raised ESR in an apparently clinically well patient is a reminder to continue to search for causes of inflammation. As the CRP was largely in normal range, this demonstrates the unique value of the ESR. In view of anti-B2 glycoprotein 1 antibody requiring to be verbally requested, discussions are ongoing with the laboratory department regarding the possibility of electronic request and a comment with recommendation to check other two antiphospholipid antibodies following one positive antibody result. As a result of this case, a plan will be put in place to ensure annual screening of antiphospholipid antibodies in all juvenile SLE patients in our care. It is hoped that this case report promotes discussion amongst the paediatric rheumatology community regarding further research required for development of paediatric specific APS criteria and management.
Abstract citation ID: rkac066.005 Introduction/Background: MDA5-positive juvenile dermatomyositis (JDM) represents a distinct clinical phenotype associated with skin and oral ulceration, milder muscle involvement and a higher incidence of interstitial lung disease (ILD) and severe rapidly progressive ILD (RP-ILD). Description/Method: The objectives were to describe the presenting clinical characteristics of patients with MDA5-positive JDM, the incidence of ILD and risk factors associated with development of RP-ILD. Retrospective clinical notes review of patients with MDA5-positive JDM managed at Great Ormond Street Hospital (GOSH) over a 24-year period.
Discussion/Results Demographics: Twenty-five patients were managed at our centre with MDA5-positive JDM. One additional patient was excluded as no notes available. Sixty-four % females. Sixty % were White British, 20% Black African, 8% Mixed, 8% Asian, 8% European and 4% South Asian. Median age of presentation was 10.0 years (IQR 6.9,12.3). Diagnostic delay was significant, with median 14 weeks (8,26) between initial symptoms and diagnosis. 24% of this cohort were also Ro-52 positive. Presentation: All patients had skin involvement; 52% ulcerating skin disease, 64% heliotrope rash and 100% Gottrons papules on initial presentation. Forty-four % had peri-ungal changes, 35% digital pitting/ infarcts and 64% nailfold changes. 40% had peri-orbital oedema. Muscle involvement was present in all, with median CMAS 40/52 (36,44) and MMT8 57/80 (51,62). Eighty-eight % had arthritis; initial active joint count was available for 16 patients with median 5.5 joints (3,16). 40% had gastrointestinal symptoms; fever, weight loss and mouth ulcers were present in 52%, 52% and 60% respectively. Twenty-four % had respiratory symptoms at diagnosis. Interstitial lung disease: 52% were diagnosed with ILD and a further 20% had abnormal pulmonary CT scans not thought to be diagnostic of ILD. 13% (2 patients) had RP-ILD; both of whom died despite immunosuppression and extracorporeal membrane oxygenation. There were no other deaths amongst this cohort. No respiratory involvement was identified in 28%. Of 19 patients who had a CT chest at diagnosis, 84% were abnormal. Only 1 patient developed respiratory involvement during disease course whilst on treatment; the other 93% with ILD had evidence of ILD at diagnosis. Out of 58 putative variables, 4 risk factors were associated with development of RP-ILD which reached statistical significance, a further 3 factors were significantly protective, as is shown in Table 1. 2 patients had pneumocystis pneumonia (PCP), both of whom required intensive care and one associated with death. Key learning points/Conclusion: Skin and muscle involvement were identified in all patients, with the majority also presenting with ulcerating skin disease, oral ulceration and arthritis. The majority of this cohort had lung involvement and 2 patients died of RP-ILD. Four risk factors were found to be predictive of RP-ILD and a further 3 protective factors were identified. Rapid deterioration of respiratory symptoms was associated with PCP, while ILD was unlikely to develop whilst on treatment if not present at diagnosis. These findings need to be validated in a larger cohort of patients. Introduction/Background: Rheumatic pain can result from a multitude of aetiologies. We present a complex case of thigh pain as the presenting manifestation of GPA, which required a multi-disciplinary approach to investigate, diagnose and manage. The pain was attributed to lumbosacral plexopathy, a rare neurological manifestation of GPA. The case was further complicated by subsequent leg weakness secondary to steroid-induced myopathy underlining the challenges confronting clinicians in diagnosing and managing complex systemic conditions. Description/Method: A 73-year-old male was admitted with severe crampy bilateral thigh and buttock pain associated with reduced exercise tolerance. He had been well, other than a past history of bladder cancer, until 4 weeks previously when he developed a prodrome, sinusitis and epistaxis. Bloods showed raised inflammatory markers, a strongly positive PR3 and a normal CK. On examination he had no synovitis and no vasculitic rash. There was tenderness around the hamstrings and ischial tuberosities. Neurological examination showed no evidence of motor weakness or sensory disturbance. Urine dip showed þ1 protein and þ1 blood with normal ACR. CT thorax showed no lung involvement. MRI head showed mild mucosal thickening in the ethmoid air cells. Nasal biopsy was inadequate, only showing granulation tissue. MRI spine showed L4/5 central canal narrowing with impingement of traversing bilateral L5 nerve roots. Nerve conduction studies and EMG showed multiple nerves with reduced amplitude on motor and sensory studies, consistent with a bilateral lumbosacral plexopathy. He was treated as systemic GPA with high dose steroids and a plan for rituximab. The patient declined rituximab over Christmas so had methylprednisolone pulses before receiving rituximab. Two weeks later he developed new proximal leg weakness, power 2/5. Repeat MRI spine was unchanged and CK was normal. ANA was weakly positive with a negative myositis blot including Jo-1. MRI thighs showed bilateral symmetrical muscle changes suggestive of acute myositis, intriguingly with onset whilst on high dose steroids. Clinical impression was a steroid myopathy; steroids were weaned and the weakness improved. Eight weeks after rituximab he had significantly improved, with resolution of epistaxis and severe thigh pain and much improved exercise tolerance, as well as inflammatory markers settling and almost normalisation of his PR3 titre. Repeat MRI thighs after a 3-month interval showed a significant reduction in muscle oedema. Discussion/Results: The thigh pain was challenging to diagnose. It is anatomically distinct from other peripheral nervous system manifestations reported in GPA, such as distal symmetrical sensory neuropathy (7-10% of GPA), or motor mononeuritis multiplex (2-12% of GPA). However, the pieces fell into place when nerve conduction study confirmed lumbosacral plexopathy. Existing literature suggests that lumbosacral plexopathy typically presents as lower back pain radiating to the leg, often worse in supine position and may be associated with abnormal sensation and weakness in the lower limbs, in keeping with the nature of his thigh pain. Albeit rare, lumbosacral plexopathy has been associated with inflammatory diseases e.g. sarcoidosis, but there is little reporting of lumbosacral plexopathy in GPA specifically. Brachial plexopathy has been reported in microscopic polyangiitis; they proposed that vasculitic arterial ischaemia leads to plexus ischaemia. Wider differentials of plexopathy include diabetic amyotrophy, paraneoplastic phenomenon, autoimmune (including CIDP), localised trauma or infection; these should be ruled out with relevant investigations. His vasculitic ENT symptoms settled with initial high dose steroids, but the excruciating thigh pain did not. When he developed thigh weakness having just received pulsed methylprednisolone, MRI thigh showed changes suggestive of acute myositis, which added another layer of complexity. Normal CK and negative myositis autoantibodies made new-onset myositis unlikely. The multi-specialty consensus was steroid-induced myopathy, which retrospectively seems most plausible as his symptoms improved with steroid reduction, as did interval MRI follow-up scan. MRI, while highly sensitive for detecting muscle disorders, has limited specificity in distinguishing the type of myopathy and therefore is rarely performed in clinical practice to diagnose steroid-induced myopathy. MRI findings must be correlated with the clinical context. If in doubt, a muscle biopsy should be sought. This would form our next line of investigation if his thigh symptoms had not settled. Key learning points/Conclusion: The International Association for the Study of Pain (IASP) has recently defined pain as ''an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage''. Acute causes of pain are varied and include local and systemic aetiologies such as inflammatory, infective, traumatic, malignant and iatrogenic. At presentation, the patient's main symptom was "excruciating severe cramping pain". This case emphasizes the importance of a thorough clinical approach comprising detailed history and examination which guided focussed investigations and discussions with specialised multidisciplinary teams (rheumatology, ENT, radiology, neurology, neurophysiology) to unravel the complexity of this clinical scenario. Whilst peripheral nervous system involvement, most frequently mononeuritis multiplex, is common in ANCA-associated vasculitis, plexopathy is not; however, discussion with the neurophysiologist was extremely helpful in interpreting complex neurophysiology tests to appreciate it was a vasculitic manifestation. As symptoms evolve, always consider if they reflect the underlying disease or are sequelae of treatment. The likelihood of developing acute myositis whilst on high dose steroids was less plausible than a steroid myopathy; always treat the patient and the clinical scenario. Interval scanning can be helpful to monitor progress and response to treatment; in this case it was reassuring that repeat MRI thigh showed a reduction in muscle oedema once steroids were decreased. Whilst "common things are common", rare presentations of rare conditions also occur; utilise the expertise of your MDT in these situations.

PAIN IN RHEUMATIC DISEASE
Abstract citation ID: rkac066.007 OA07 WHAT IS EFFECTIVE PAIN MANAGEMENT: AN idge University Hospitals NHS umatology, Cambridge University Hospitals NHS Foundation Trust, and 3 Division of Medicine, University of Cambridge Introduction/Background: Pain is a sensory and emotional experience perceived in terms of tissue damage and expressed in terms of altered behaviour. Chronic, medically unexplained pain is complex, disabling and common. It is important to rule out medical or modifiable causes, but most tests will not result in significant changes in management nor prognosis. Attempting rehabilitation before the patient narrative has been fully explained usually leads to a lack of progress. Sleep deprivation is important to acknowledge and restorative sleep has analgesic and fatigue-improving properties. Prior mood disturbances may alter management, particularly if bereavement or post-traumatic memories are present. Adverse childhood events occur more frequently than expected in this population. Somatisation and personality disorders will need expert evaluation and management. Significant anxiety and depression should be managed independent of pain report. Physical rehabilitation is effective in restoring function which can lead to a recovery of identity and workplace productivity. Altering health beliefs and cognition can be important as part of this process. Exercise prescriptions and access to support during this process are also important. Analgesic medications usually have little to offer other than side effects, but can be used to bridge difficult times, particularly if patient expectations align with their use. Strong opioids should not be started, unless no other options are available, and always with a time-and dose-limit, preferably less than 50mg daily of morphine equivalent for less than 3 months. We present the case of a young gentleman of working age with chronic back pain who underwent effective pain management to restore good function including a full return to work, improvement in his mood, sleep, physical function and quality of life. Description/Method: 43 year old manager working as a Risk Manager developed back pain without trauma that affected all three segments. There was no morning stiffness, night pain nor gelling history. His pain was worse on exercise and when standing. The pain was intrusive and affecting his quality of life, to the extent that he could not attend work. Time away from the workplace was adding stress and affecting his mood and, intermittently, his sleep. There was no history of night sweats, weight loss, loss of appetite, significant leg pain nor numbness in his feet nor saddle area. There was no loss of control in his bowel nor urine habit. His blood tests (FBC, LFT, Creat, ESR, CRP, vitamin D, ESR, CRP) were normal. An MRI scan of his whole spine showed minor degenerative disc changes but no significant bone changes nor neural compression. His medications were sertraline 50mg once daily, meloxicam 7.5mg once daily and omeprazole 20mg once daily. The pain management programme teaches self-management approaches to patients experiencing chronic pain. It is delivered by a physiotherapist, an occupational therapist, a nurse and a clinical psychologist. Its aim is to help patients to maintain or increase their physical functioning and to regain their sense of control in the context of their life. In turn, patients may improve in their well-being and their quality of life, despite their chronic pain. The programme runs for twelve days with patients attending as out-patients, four days a week for three weeks. Reviews take place at one month, six months and one year following this.
i4 https://academic.oup.com/rheumap Discussion/Results: Table 1 outlines the improvement in his outcomes. Self-efficacy scores rose first with associated drops in catastrophisation and kinesiophobia. Anxiety and depression scores also dropped after the first 6 weeks. Pain significantly reduced along with improvements in quality of life and return to full employment 6 months later. Key learning points/Conclusion: Patients with chronic pain have significant disability, poor quality of life and are not economically productive. Pain management programmes are well evidenced to restore function and improve quality of life. Pain scores typically drop later and full employment can be regained, thus suggesting a cost-effectiveness of such programmes for a population. In patients who do not achieve remission in all disease aspects on biologic monotherapy or combination of a biologic therapy with an oral synthetic agent; dual targeted anti-cytokines strategies or combined biologic with a targeted oral small molecule are a possible treatment option. Description/Method: A 40-year-old attended our rheumatology department in 2010 with peripheral synovitis, dactylitis and scalp psoriasis. A clinical diagnosis of PsA was made and she was commenced on combination methotrexate and sulphasalazine. In 2011, therapy was escalated to include etanercept and methotrexate due to persistent active disease clinically and on nuclear medicine bone scan. Between 2011 to 2015, sequential bDMARD switches including certolizumab, infliximab and adalimumab, failed to put the disease in remission.

PSORIATIC ARTHRITIS
Due to loss of effect, adalimumab was switched to secukinumab in early 2016. A few months later, while on secukinumab, she developed new onset Crohn's disease and required treatment change to ustekinumab. In August 2018 following a prolonged flare, ustekinumab was stopped and tofacitinib was started. The disease went in LDA until September 2020 when hospital admission for a severe PsA flare was required. She had dactylitis of 3 digits, a left temporomandibular joint effusion on ultrasound and elevated acute phase reactants. A treatment change to abatacept resulted in primary failure and abatacept was replaced with baricitinib.
In March 2021, she attended clinic with new nail changes, dactylitis of 3 digits and a large left knee effusion. She underwent a diagnostic arthroscopy of the left knee and wash-out in May 2021 which showed a macroscopic synovitis score and vascularity score of 100% respectively. Synovial histology showed evidence of chronic synovitis with abundant plasma cells.
Following the arthroscopy and careful discussion, it was decided to initiate combination therapy with adalimumab biosimilar and tofacitinib in June 2021. The patient was assessed at 2 months following starting combination therapy and a dramatic clinical and biochemical was noted. CRP had improved from 139.9mg/L to 6.3mg/L. She was mobilising without an aid for the first time in years. Both her psoriasis and Crohn's disease were also well controlled. Discussion/Results: While the outcomes of patients with psoriasis have dramatically improved with monoclonal antibody therapies targeting IL-23 and IL-17A; achieving a measurable low disease activity state such as minimal disease activity (MDA) for musculoskeletal manifestations of psoriatic disease is infrequent. Due to the heterogeneity of disease in PsA, multiple cellular pathways are involved in the pathogenesis resulting in recalcitrant disease in a subgroup of patients. These patients, like our case, exhibit poor response to the current therapeutic paradigm in PsA.
In such patients, treating one disease domain, one type of cell or a single pathway at a time is unlikely to result in meaningful disease control and remission may be unachievable thus subjecting patients to sustained joint inflammation and damage seen in PsA. Very little data exist regarding the safety of dual immunomodulator therapies for concomitant psoriasis and psoriatic arthritis. Safety concerns such as infectious risks are important considerations with such strategies; however, the targeted second-generation anti-cytokine biologics and targeted JAK-I have exhibited improved safety profiles with regards to infections. In this case, following careful discussion with our patient, she felt that the prospect of possible reduction in her musculoskeletal symptoms outweighed the potential safety concerns. Multiple cases are reported in the literature regarding the use combined biologic strategies in psoriatic disease; the most common combination reported being anti-TNF therapy and ustekinumab with varying degrees of response. Prospective, high-quality studies are needed to identify safe and efficacious dual strategies in PsA to pinpoint dosages, sequence and frequency of therapies. Key learning points/Conclusion: This case truly highlights the heterogeneity and complexity that accompanies psoriatic disease and as such, modulating a single pathway may not be sufficient to address all the phenotypic domains (skin, synovium, entheses, and axial). While physicians are often, understandably, hesitant to prescribe combined immunomodulatory therapies due to concerns regarding potential complications, such strategies should be considered in debilitating cases of psoriatic disease who fail to respond to conventional treatment as they have the potential to foster deep and long-lasting remission.
Our case highlights that a patient-centred approach with patient involvement in clinical decisions regarding their disease is required. With such strategies, patients and clinicians, both, should balance the potential associated risks particularly infectious risk. Further studies are required to better determine the efficacy and safety profile of combined immunomodulatory therapies in psoriatic disease.
Abstract citation ID: rkac066.009 OA09 CHALLENGING CASE OF PSORIATIC ARTHRITIS: WHAT SHOULD WE DO NEXT?
Marwa Mohareb, Anupama Nandagudi Basildon and Thurrock Hospital, Basildon, United Kingdom Introduction/Background: Psoriatic arthritis (PsA) is a chronic inflammatory enthesoarthro-osteopathy associated with extra-articular manifestations and several co-morbidities occurring in up to 42% of