EP23 Symptomatic sarcoid myopathy: a rare extra-pulmonary manifestation of sarcoidosis

Abstract Case report - Introduction Sarcoidosis is a multisystem disorder of unknown aetiology that is characterised pathologically by the presence of non-caseating granulomata. The disease is known for its multitude of presentations and can affect almost any organ system. Symptomatic skeletal muscle involvement in sarcoidosis is infrequent and occurs in < 3% of all sarcoidosis patients. We present the case of a 47-year-old male with multisystem sarcoidosis involving his lungs, eyes, and liver, who presented to our tertiary sarcoid centre with proximal muscle weakness. This case is significant as it highlights the diagnostic challenges that can arise when muscle weakness occurs on a background of sarcoidosis. Case report - Case description A 47-year-old gentleman presented to Rheumatology with a ten-year history of progressive lower extremity muscle weakness. He was known to have multisystem sarcoidosis affecting his lungs (diffuse interstitial lung disease), eyes (anterior uveitis) and liver (liver fibrosis). His sarcoidosis was initially diagnosed ten years beforehand, from confirmatory histology obtained via Endobronchial Ultrasound sampling. He was previously a keen runner; however, he had observed a gradual decline in his ability to run. Over a period of two years his mobility further deteriorated, and he required two sticks to walk. Physical examination revealed a waddling gait with wasting to his quadriceps bilaterally. He had reduced power of 2/5 on hip flexion on the Medical Research Council (MRC) muscle grading scale. There was no bulbar involvement and facial and upper extremity strength was normal. His past medical history was also remarkable for anxiety and depression. There was no family history of muscle disease. Serology revealed a Creatine Kinase (CK) of 773 IU/L (32-294 IU/L). He had an equivocal signal recognition particle (SRP) antibody result, which was later repeated and found to be negative. His EMG showed myopathic changes in his distal and proximal lower limb muscles with profuse spontaneous activity, indicating an active myopathic process. MRI of his lower limbs showed symmetrical fatty infiltration in the distal semimembranosus and short head of biceps femoris muscles with no clear oedema. A muscle biopsy showed diffuse MHC Class 1 upregulation with nemaline rods. Treatment with pulsed IV methylprednisolone was started, in addition to Mycophenolate Mofetil (MMF) as steroid therapy was not sufficient to suppress his disease. He had a reduction in his CK to 205 IU/L and no activity in his skeletal muscle on FDG-PET CT. His power improved to 3/5 on MRC grading. Case report - Discussion Three distinct patterns of muscle involvement in sarcoidosis are recognised: chronic myopathy, nodular myopathy, and acute myopathy. Symptomatic muscle disease in sarcoidosis is rare and it is important to consider other potential aetiologies of a progressive myopathy, even in a patient with established multisystem sarcoidosis. This case is interesting as there was diagnostic difficulty in ascertaining the diagnosis, which potentially included a corticosteroid-induced myopathy, SRP necrotising myopathy, or even a nemaline myopathy. Corticosteroid myopathy has a similar distribution to a sarcoid myopathy. However, the patient’s clinical phenotype, elevated muscle enzymes, EMG findings, and histological data favoured an inflammatory myositis. SRP necrotising myopathy is characterised by rapidly progressive proximal muscle weakness with necrotic muscle fibres, scant inflammation, and a significant elevation in muscle enzymes, which were not seen in this patient. The patient’s weakness was more insidious in onset, with diffuse inflammation on muscle biopsy. Nemaline rods were seen on biopsy, however these were only present in one area, which is atypical of a nemaline myopathy. Furthermore, the presence of many loculated fibres on biopsy and upregulation of MHC class 1 was more in keeping with a diagnosis of an inflammatory myopathy secondary to sarcoidosis, even in the absence of non-caseating granulomas on muscle biopsy. There are no randomised controlled trials of treatments in sarcoid myopathy. While methotrexate is most used in steroid-recalcitrant myositis, the patient’s liver fibrosis preluded this therapy, thus MMF was trialled instead. Co-existing inflammatory muscle disease with sarcoidosis has been documented infrequently in the literature. They both have overlapping symptoms with contrasting treatment strategies. In this patient, the muscle biopsy pointed to an idiopathic inflammatory myopathy (IIM) without granulomatous infiltration, it is intriguing to consider whether treatment of an IIM with intravenous immunoglobulin or rituximab would have resulted in better clinical outcomes. Case report - Key learning points Key points: Even though symptomatic muscle involvement in sarcoidosis is uncommon, a sarcoid myopathy should be suspected in symptomatic patients with known or suspected pulmonary or extrapulmonary sarcoidosis. In patients without known sarcoidosis but with unexplained muscle symptoms, particularly in the setting of a multisystem illness, sarcoid myopathy should be considered in the differential diagnosis. MRI and muscle biopsy are useful in distinguishing a sarcoid myopathy from a corticosteroid-induced myopathy as illustrated in this case. Fluorine 18 fluorodeoxyglucose (FDG) PET/CT is sensitive for assessment of the inflammatory activity of sarcoidosis in any organ. In this patient, FDG-PET was useful in evaluating active sarcoid lesions and evaluating the therapeutic effects of Mycophenolate Mofetil on his sarcoid myopathy. Although there is limited data to guide treatment in a sarcoid myopathy, Mycophenolate Mofetil can be used as an alternative to Methotrexate.

The patient has had several episodes of psychosis and confusion which were previously diagnosed as schizophrenia and corticosteroid induced psychosis, meaning the team used steroids cautiously. MRI brain imaging revealed the presence of extensive neurosarcoidosis, and the neurocognitive improvement with treatment of a TNF inhibitor, suggested that the underlying pathology was sarcoidosis. Steroids could therefore be utilised appropriately for ongoing management. This case illustrates the difficulty of teasing out the underlying aetiology of neurocognitive dysfunction in patients with extensive sarcoidosis. TNFa released by alveolar macrophages is implicated in the induction and maintenance of sarcoid granulomas. Limited data from small randomised controlled trials and increasing data from non-randomised studies have led to consensus-based recommendations for TNFi use in pulmonary, ocular, cutaneous, neurological, and multi-system sarcoidosis. To our knowledge, this case is the first documented example of rapid clinical and radiological resolution of sarcoid myositis with an anti-TNF agent. Case report -Key learning points: There are three important points to take away from this case. First, this case highlights the importance of a PET scan in demonstrating multi-system involvement in sarcoidosis. The PET scan was key in highlighting the extent of disease including sarcoid myositis. MRI scans of the brain were also important in highlighting the extent of neurosarcoidosis. Second, thepatientpresentedwithpsychosisin2013.Thiswasthoughtto be corticosteroid-induced at the time. However, since treatment with the TNF inhibitor the patient experienced a significant neurocognitive improvement. Thedrasticimprovementunderminesthediagnosisofprimarypsychosisand suggests that the psychosis may have been due to neurosarcoidosis. In the context of patients with multi-organ sarcoidosis, psychosis secondary to neurosarcoid should be considered as a differential, even in the context of an earlierdiagnosisofschizophreniapre-datingthediagnosisofsarcoid. Third, the drastic resolution of sarcoid myositis and arthritis with a TNF inhibitor suggests that TNF inhibitors should be considered as treatment for cases of sarcoid myositis or sarcoid arthritis refractory to steroids. Whilst TNF inhibitors are currently unlicensed for this use in the UK, there is a growing body of evidence for their effectiveness in treating refractory extra-pulmonary sarcoidosis.

Rajiv Ark Royal Lancaster Infirmary, Lancaster, United Kingdom
Case report -Introduction: In 2011 a gentleman in his 50s presented with nasal blockage and bloody discharge. He was diagnosed with sarcoidosis and after 9 years of failed strategies to control his disease, he developeddactylitis. X-ray of the hands showed severe arthropathy in the distal interphalangeal joints. This case demonstrates an uncommon extrapulmonary manifestation of sarcoidosis. Although most of his follow up was with a respiratory clinic, his main symptoms were not due to interstitial lung disease, highlighting the importance of a multidisciplinary approach. To reduce the need for steroids, several DMARDs were tried illustrating that there arelimited treatment options. Case report -Case description: This gentleman presented in June 2011 with left epiphora, bloody nasal discharge and fatigue. He had no family history of sarcoidosis and was of Caucasian ethnicity. He was referred by his GP to Ophthalmology and ENT. Septoplasty showed a 95% blockage at the lacrimal sac. A biopsy was performed, and histology showed a nasal sarcoid granuloma. He was referred to the respiratory team who requested a high-resolution CT scan showing sizeable lymph nodes. One inguinal node was biopsied confirming sarcoid granulomas before starting treatment. Calcium was briefly raised, and serum ACE was initially 123. He was started on 40mg of prednisolone for 6 weeks, which was tapered to 20/25mg on alternating days. There was a recurrence of his nasal discharge; steroids were increased again but he developed symptoms of muscle weakness from long term steroid use. He was referred to an interstitial lung disease clinic at a tertiary centre where he was investigated for cardiac sarcoidosis with MRI due to ventricular ectopics. Hydroxychloroquine was started to reduce the steroid use however he developed symptoms of tinnitus, so it was stopped. Methotrexate, Azathioprine and Leflunomide were all trialled to however they did not have any impact on controlling his disease. His Prednisolone was slowly reduced by 1mg a month. When he had recurrence of his symptoms, he was given IVmethylprednisolone. Nine years after his first presentation he presented with stiffness of the right thumb base. This progressed to dactylitis and slight fixed flexion deformity of rightindex fingerand left little finger. An x-ray of his hands showed disease in the distal interphalangeal joints bilaterally with severe changes in the left little finger. The effects of longterm steroids led him to request aletterto support early retirement.
Case report -Discussion: The main rationale for changing treatment options was to reduce the prednisolone dose. Steroids were the only treatment option that showed evidence of controlling his disease when the dose was between 25mg and 40mg a day. Each of the DMARDs that were trialled had a different side effect profile and did not show any evidence of suppressing disease as symptoms recurred. Dose changes later in treatment fluctuated, reflecting a balancing act between disease recurrence and sideeffects of long-term steroids. There are many extra pulmonary manifestations of sarcoidosis that were investigated in this case. The first being the nasal granuloma, which can occur in sarcoid patients with symptoms of epistaxis, crusting, congestion, and pain. There were granulomatous changes seen in the hila as wellas other lymph nodes such as the inguinal region; inguinal lymphadenopathy can lead to pain in the groin area. In addition to this it was important to exclude uveitis with ophthalmology review as he had symptoms of epiphora. Uveitis can be diagnosed in ophthalmological assessment of sarcoid patients in the absence of ocular complaints. Cardiac sarcoidosis was excluded with an MRI at a specialist heart and lung centre due to ventricular ectopics. Cardiac sarcoidosis can lead to heart block, arrhythmias, and congestive cardiacfailure. Finally, he developed sarcoid arthropathy, review of his radiological imagesover time showed extensive damage to the jointsof the hand. This gentleman had poor outcomes due to limited treatment options for his disease. Being restricted to long term steroid as the mainstay of treatment led to early retirement due to fatigue and muscle weakness. Conversely, under dosing steroids led to recurrence in symptoms. His disease is still not controlled as shown by an evolving sarcoid arthropathy. Case report -Key learning points: An illustration of sarcoid arthropathy is also shown in this case. Sarcoid arthropathy is an uncommon manifestation of the disease primarily affecting joints in the hands and feet. In this case the distal interphalangeal joints and proximal interphalangeal joints were affected. The first symptom of arthropathy was stiffness of the base of the right thumb in 2017, this could fit with an osteoarthritic picture and could be mistaken for it in undiagnosed sarcoidosis. The most severe disease was in the DIP of the left little finger, which is not commonly affected. An oligoarthritic pattern with involvement of the ankle is seen more often. This is also an unusual case of sarcoidosis as there was no family history of the disease and his ethnicity did not predispose him to the condition. He also had a few uncommon extra pulmonary manifestations of sarcoidosis. The importance of a multidisciplinary approach in managing sarcoidosis wasdemonstratedinthiscase.Mostofhisfollowupwaswitharespiratory clinic. However, respiratory symptoms were not the main issue during the patient journey; early ENT and rheumatology input was significant inmanaging his disease. Although pulmonary lymph nodes were enlarged, they did not affect hislung function.

Saadia Sasha Ali, Mark Russell, James Galloway and Ioana Onac
King's College Hospital, London, United Kingdom Case report -Introduction: Sarcoidosis is a multisystem disorder of unknown aetiology that is characterised pathologically by the presence of non-caseating granulomata. The disease is known for its multitude of presentations and can affect almost any organ system. Symptomatic skeletal muscle involvement in sarcoidosis is infrequent and occurs in < 3% of all sarcoidosis patients. We present the case of a 47-year-old male with multisystem sarcoidosis involving his lungs, eyes, and liver, who presented to our tertiary sarcoid centre with proximal muscle weakness. This case is significant as it highlights the diagnostic challenges that can arise when muscle weakness occurs on a background of sarcoidosis. Case report -Case description: A 47-year-old gentleman presented to Rheumatology with a ten-year history of progressive lower extremity muscle weakness. He was known to have multisystem sarcoidosis affecting his lungs (diffuse interstitial lung disease), eyes (anterior uveitis) and liver (liver fibrosis). His sarcoidosis was initially diagnosed ten years beforehand, from confirmatory histology obtained via Endobronchial Ultrasound sampling. He was previously a keen runner; however, he had observed a gradual decline in his ability to run. Over a period of two years his mobility further deteriorated,and herequiredtwo sticks to walk. Physical examination revealed a waddling gait with wasting to his quadriceps bilaterally. He had reduced power of 2/5 on hip flexion on the Medical Research Council (MRC) muscle grading scale. There was no bulbar involvement and facial and upper extremitystrength was normal.

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https://academic.oup.com/rheumap i28 EPOSTER His past medical history was also remarkable for anxiety and depression. There was nofamilyhistory of muscle disease. Serology revealed a Creatine Kinase (CK) of 773 IU/L (32-294 IU/L). He had an equivocal signal recognition particle (SRP) antibody result, which was later repeated and found to be negative. His EMG showed myopathic changes in his distal and proximal lower limb muscles with profuse spontaneous activity,indicating anactive myopathicprocess. MRI of his lower limbs showed symmetrical fatty infiltration in the distal semimembranosus and short head of biceps femoris muscles with no clear oedema. A muscle biopsy showed diffuse MHC Class 1 upregulation with nemaline rods. Treatment with pulsed IV methylprednisolone was started, in addition to Mycophenolate Mofetil (MMF) as steroid therapy was not sufficient to suppress his disease. He had a reduction in his CK to 205 IU/L and no activity in his skeletal muscle on FDG-PET CT. His power improved to 3/5 onMRCgrading.
Case report -Discussion: Three distinct patterns of muscle involvement in sarcoidosis are recognised: chronicmyopathy, nodular myopathy, and acute myopathy. Symptomatic muscle disease in sarcoidosis is rare and it is important to consider other potential aetiologies of a progressive myopathy, even in a patient with established multisystem sarcoidosis. This case is interesting as there was diagnostic difficulty in ascertaining the diagnosis, which potentially included a corticosteroid-induced myopathy, SRP necrotising myopathy, oreven anemaline myopathy. Corticosteroid myopathy has a similar distribution to a sarcoid myopathy. However, the patient's clinical phenotype, elevated muscle enzymes, EMG findings, and histological data favoured an inflammatorymyositis. SRP necrotising myopathy is characterised by rapidly progressive proximal muscle weakness with necrotic muscle fibres, scant inflammation, and a significant elevation in muscle enzymes, which were not seen in this patient. The patient's weakness was more insidious in onset, with diffuse inflammation on muscle biopsy. Nemaline rods were seen on biopsy, however these were only present in one area, which is atypical of a nemaline myopathy. Furthermore, the presence of many loculated fibres on biopsy and upregulation of MHC class 1 was more in keeping with a diagnosis of an inflammatory myopathy secondary to sarcoidosis, even in the absence of non-caseating granulomas onmuscle biopsy. There are norandomised controlled trials of treatments insarcoid myopathy. While methotrexate is most used in steroid-recalcitrant myositis, the patient's liver fibrosis preluded this therapy, thus MMF was trialled instead. Co-existing inflammatory muscle disease with sarcoidosis has been documented infrequently in the literature. They both have overlapping symptoms with contrasting treatment strategies. In this patient, the musclebiopsy pointed toanidiopathic inflammatorymyopathy (IIM)without granulomatous infiltration, it is intriguing to consider whether treatment of an IIM with intravenous immunoglobulin or rituximab would have resulted in better clinical outcomes. Case report -Key learningpoints: Keypoints: Even though symptomatic muscle involvement in sarcoidosis is uncommon, a sarcoid myopathy should be suspected in symptomatic patients with known or suspected pulmonary or extrapulmonary sarcoidosis. In patients without known sarcoidosis but with unexplained muscle symptoms, particularly in the setting of a multisystem illness, sarcoid myopathy should be considered in the differential diagnosis. MRI and muscle biopsy are useful in distinguishing a sarcoid myopathy from a corticosteroid-induced myopathy as illustrated in this case. Fluorine 18 fluorodeoxyglucose (FDG) PET/CT is sensitive for assessment of the inflammatory activity of sarcoidosis in any organ. In this patient, FDG-PET was useful in evaluating active sarcoid lesions and evaluating the therapeutic effects of Mycophenolate Mofetil on his sarcoid myopathy. Although there is limited data to guide treatment in a sarcoid myopathy, Mycophenolate Mofetil can be used as an alternative to Methotrexate.

Ritsuko Saito and Ernest Wong
Queen Alexandra Hospital, Portsmouth, United Kingdom Casereport-Introduction:Granulomatousdisordersarediverseintheir aetiologies and presentations. We present an unusual case of severe psoriatic arthritis patient who subsequently developed multiple granulomatous diseases over time, granulomatous interstitial nephritis, granulomatous sarcoidosis with hilar lymphadenopathy and localised laryngeal granulomatous inflammation secondary to lambda type amyloidosis.
Case report -Case description: 52-year-old gentleman with arthritis mutilans secondary to severe poorly controlled psoriatic arthritis was followed up in Rheumatology clinic. Earlier therapy with leflunomide and methotrexate provided inadequate control. Golimumab, despite giving a good response, was stopped in 2013 after 5 months of treatment due to acute kidney injury. Renal biopsy revealed granulomatous interstitial nephritis, thought to be Golimumab-induced based on the timing of usage and reversibility with discontinuation. He was then trialled on UstekinumabandSecukinumabin2016 and2017respectively with variable response.
He also had a few-years history of voice change (high pitched) and sore throat which he attributed to recurrent colds. He denied dysphagia or breathlessness, and he did not have stridor. He has never smoked and only drank alcohol occasionally. ENT team noted white deposits on erythematous and thickened false vocal cords and posterior glottis with a thin web on microlaryngoscopy, which histologically proved to show granulomatous inflammation, potentially consisting of amyloid, although congo red stain was negative. On further investigation, including SAP scan, he was diagnosed with localised lambda type amyloid. Increasing throat pain and worsening dysphonia prompted change of management from conservative to a surgery at a specialist centre and an input from speech and language therapy team. During thistime,considerationforEtanerceptforhisjointandskindisease was put on hold, pending further management of laryngeal amyloidosis. Furthermore, he presented to hospital with breathlessness in 2019, where his chest X-ray showed bulky right hilum and a follow-up CT chest revealed calcified right hilar and mediastinal lymphadenopathy, ground glass opacification and consolidation. Histology from hilar node was suggestive of sarcoidosis,with stain negative foramyloid. He underwent removal of false vocal cords for his symptomatic laryngeal amyloidosis. He continues to be followed up at the local Rheumatology, Dermatology and ENT team. Case report -Discussion: Granulomatous diseases have vast aetiologies, including infectious, immunological, neoplastic, and chemicalinduced processes. The age at which they affect patients and tissue they involve also vary hugely. This is the first reported case of three seemingly unrelated granulomatous diseases occurring in a single patient with severe refractory psoriatic arthritis. Retrospective reassessment of the histology samples supported that these are three separate pathologies. It is very unusual for one patient to acquire multiple separate granulomatous diseases, which was why the diagnostic process of this patient was challenging. In this case, managing the original underlying psoriatic arthritis was particularly difficult due to interruptions of treatment for adverse drug effects and investigations and treatment of subsequent granulomatous diseases. The case also raises questions about possible currently unknown association between the pathologies. Case report -Key learning points: Key points are the uniqueness of this case and that it highlighted the possibility of currently under-reported association between these three granulomatous conditions. As ever, a multidisciplinary approach to managing such a complex patient is important forthe provision of good care.
EP25 BLAU SYNDROME: A LIFETIME OF SARCOID Case report -Introduction: Here we explore a case of a 31-year-old female treated with juvenile arthritis rebranded as Blau syndrome. This is characterised by sarcoid involvement principally of her eyes as well as skin, kidneys, and joints. We aim to explore her management challenges and complications. Case report -Case description: 31 MS of Afro-Caribbean descent was diagnosed with early onset sarcoidosis at the age of 18 months. She was later found to be NOD2 gene positive but has no significant family history. Her health has been further complicated by her diagnoses of growth hormone deficiencyand hyperthyroidism secondary to multinodulargoitre. Clinically MS has a short stature and profound deafness. A legacy of the ophthalmic morbidity, panuveitis, has led to a visual acuity is 6/15 in her left eye and her right reduced to counting fingers due to developing endophthalmitis in 2019. Her arthritis is stable, but there are flexion deformities primarily involving her proximal interphalangeal joints reducing her grip function. In adulthood she does not have significant cutaneous changes.
Investigations have revealed her to be anti-nuclear and anti-neutrophil cytoplasmic antibody negative. Radiologically, hand films show sparing of erosive changes, radiocarpal subluxation, and deformity of carpi in