EP16 Challenges in treating new onset systemic lupus erythematosus with lupus nephritis and COVID-19 infection overlap

Abstract Case report - Introduction COVID-19 infection caused by a novel coronavirus SARS-coV-2 has made the diagnosis and the treatment of inflammatory diseases incredibly challenging. On the one hand, because of its pro-inflammatory state, that may aggravate or trigger flares in autoimmune diseases such as systemic lupus erythematosus (SLE). On the other hand, the risk of an immunosuppressive therapy during the active phase SARS-coV-2 infection that may lead to catastrophic outcomes. We report a case of a 24-year-old female newly diagnosed with SLE during COVID-19 pandemic who developed COVID-19 infection during her induction treatment for lupus nephritis. Case report - Case description A 24-year-old Nepali female, with no past medical history of note, presented to her regional hospital with a history of flu-like symptoms few days ago, peripheral oedema, acute kidney injury with proteinuria and hypertension. Further investigations showed a high titre of double-stranded DNA antibodies, anti-cardiolipin IgM and B2 microglobulin positive and low C3. She also developed a haemolytic anaemia and thrombocytopenia during her admission. She received pulsed steroid therapy and was started on mycophenolate mofetil (MMF) for a probable lupus nephritis awaiting the results of biopsy, which showed later a lupus nephritis Class IV-G with active lesions. She then developed symptoms of COVID-19 infection and had a positive PCR leading to an interruption of her induction therapy. She was recruited to the RECOVERY trial on the lopinavir-ritonavir arm and made a good recovery. Case report - Discussion It is well known that viruses can trigger or aggravate auto-immune response in patients predisposed genetically. However, the role of SARS-coV-2 is not elucidated yet. The EULAR COVID-19 registry showed that rheumatoid arthritis and SLE were the most prevalent rheumatic diseases, and there was an increased risk in those who are on moderate to high dose corticosteroids. In patients with SLE and COVID-19 infection, it is agreed by all the national and international rheumatology societies to interrupt their immunosuppressive therapy until the symptoms resolve, especially those with renal involvement or an active disease. Which is the case in our patient. Luckily, she resumed her MMF a month later after a negative PCR and her renal function has continued to improve. Case report - Key learning points Lupus nephritis is a major risk factor for overall morbidity and mortality in SLE. It requires an early immunosuppressive treatment to induce remission. Randomized clinical trials showed that MMF is at least equally effective as cyclophosphamide in inducing remission and that it has been associated with a reduced risk of infection and amenorrhea. It seems to be a suitable alternative in women of childbearing age. In patients with concomitant COVID-19 disease, immunosuppressive therapy should be paused until the symptoms improve.

Vasculitis including aortitis can be a complication of  infection. Endothelial cell inflammation is likely to play key role in the pathogenesis of COVID-19 associated vasculitis. In addition to corticosteroids, other immune-modulating drugs presently used in rheumatology may be effective therapeutic agents. Case report -Introduction: We describe an acute onset self-limiting seronegative non-destructive symmetrical polyarthritis five weeks after laboratory confirmed COVID-19 infection.
Case report -Case description: A 37-year-old male hospital doctor of presented to the Early Inflammatory Arthritis clinic with a four-week history of acute onset joint pain, swelling and early morning stiffness in excess of two hours. The symptoms began at the left ankle with Achilles' tendonitis but progressed over the following 72 hours to a symmetrical polyarthritis affecting the wrists, proximal interphalangeal joints, shoulders, elbows, and knees. Approximately five weeks prior to the onset of his joint symptoms he had laboratory confirmed SARS-CoV-2 infection with six days of fever, nonproductivecough, and fatigue. He did not requirehospitalisation.
His past medical history was significant for biopsy proven non-alcoholic fatty liver disease. There was no prior history of inflammatory arthritis and no personal or family history of skin psoriasis, inflammatory bowel disease or uveitis. There was no preceding genitourinary or gastrointestinal upset. His family history was significant for a sister with seronegative rheumatoid arthritis for which shewas takingsulfasalazine. Examination revealed a normal BMI, synovitis at the wrists and proximal interphalangeal joints without evidence of joint effusion in the large joints. Blood tests revealed elevations in the ESR (83 mm/hour, reference range 0-10 mm/hour) and CRP (25mg/dL, reference range <5mg/dL). Serology was negative for the rheumatoid factor, anti-CCP antibodies, antinuclear antibodies, and an extractable nuclear antigen panel. Radiographs of the affected joints were unremarkable. Serological testing was positive for anti-SARS-CoV-2 IgG antibodies. He was started on oral Prednisolone 20mg daily and an NSAID with good symptomatic response and normalisation of his ESR (5mm/hour) and CRP (<1mg/dL). The course of prednisolone was tapered over a 6-week period and he is still in steroid free remission with normal inflammatory markers at follow up. The patient was given a diagnosis of a post-viral reactive arthritiswhichwas attributed to the preceding COVID-19 illness.
Interestingly, viral arthritis has not been reported in influenza and human coronaviruses (including SARS and MERS). Arthralgia was reported in 14.9% of laboratory confirmed COVID-19 cases in China during the early phases of the pandemic but inflammatory arthritis was not well described.
The clinical course of the inflammatory arthritis in this case was self-limiting with enthesitis and synovitis resolving within six weeks of onset with the mainstay of treatment being symptomatic relief in the form of nonsteroidal anti-inflammatory drugs and corticosteroids. Patient perspective: When I woke up that Tuesday morning with severe joint pains and stiffness, I knew something was not right. It was not like anything I have felt before in terms of my joints, having had sports injuries in the past. It was to the point where I was even struggling to go from sitting to standing. Without Prednisolone, I feel as if I would not have been able to work and may even have been house bound. I was relieved that this inflammatory arthritis did respond to Prednisolone. After six weeks of taking Prednisolone, the condition seemed to settle. Case report -Key learning points: A self-limiting episode of inflammatory arthritis may occur following COVID-19 infection.

EP16 CHALLENGES IN TREATING NEW ONSET SYSTEMIC LUPUS ERYTHEMATOSUS WITH LUPUS NEPHRITIS AND COVID-19 INFECTION OVERLAP
Selma Dahou 1,2 , Tim Leach 1,2 , Kathryn Bostock 1,2 , Jonathan Louden 1,2 , Jonathan Raj 1,2 and Shivan Ghedia 1,2 1 Queen Alexandra University Hospital, Portsmouth, United Kingdom, and 2 Wessex Kidney Centre, Portsmouth, United Kingdom Case report -Introduction: COVID-19 infection caused by a novel coronavirus SARS-coV-2 has made the diagnosis and the treatment of inflammatory diseases incredibly challenging. On the one hand, because of its pro-inflammatory state, that may aggravate or trigger flares in autoimmune diseases such as systemic lupus erythematosus (SLE). On the other hand, the risk of an immunosuppressive therapy during the active phase SARS-coV-2 infection that may lead to catastrophic outcomes. We report a case of a 24-year-old female newly diagnosed with SLE during COVID-19 pandemic who developed COVID-19 infection during her inductiontreatment forlupus nephritis. Case report -Case description: A 24-year-old Nepali female, with no past medical history of note, presented to her regional hospital with a history of flu-like symptoms few days ago, peripheral oedema, acute kidney injury with proteinuria and hypertension. Further investigations showed a high titre of double-stranded DNA antibodies, anti-cardiolipin IgM and B2 microglobulin positive and low C3. She also developed a haemolytic anaemia and thrombocytopenia during her admission. She received pulsed steroid therapy and was started on mycophenolate mofetil (MMF) for a probable lupus nephritis awaiting the results of biopsy, which showed later a lupus nephritis Class IV-G with active lesions. She then developed symptoms of COVID-19 infection and had a positive PCR leading to an interruption of her induction therapy. She was recruited to the RECOVERY trial on the lopinavir-ritonavir arm and made a good recovery.
Case report -Discussion: It is well known that viruses can trigger or aggravate auto-immune response in patients predisposed genetically. However, the role of SARS-coV-2 is not elucidated yet. The EULAR COVID-19 registry showed that rheumatoid arthritis and SLE were the most prevalent rheumatic diseases, and there was an increased risk in those who are on moderate to high dose corticosteroids. In patients with SLE and COVID-19 infection, it is agreed by all the national and international rheumatology societies to interrupt their immunosuppressive therapy until the symptoms resolve, especially those with renal involvement oranactive disease. Which isthe case inourpatient. Luckily, she resumed her MMF a month later after a negative PCR and her renal function has continued to improve. Case report -Key learning points: Lupus nephritis is a major risk factor for overall morbidity and mortality in SLE. It requires an early immunosuppressive treatment to induce remission.
Randomized clinical trials showed that MMF is at least equally effective as cyclophosphamide in inducing remission and that it has been associated with areduced risk of infection and amenorrhea. It seemsto be asuitable alternative in women of childbearing age. In patients with concomitant COVID-19 disease, immunosuppressive therapy should be pauseduntilthe symptoms improve.

Mid Yorkshire NHS, Wakefield, United Kingdom
Case report -Introduction: Sarcoidosis is an autoimmune, multi-system condition in which the formation of non-caseating, granulomas is a key histological feature. Clinical presentation can be variable and may lead to a delay in recognition. Most cases will resolve with minimal or no intervention. Awareness of the condition and features helps guide longterm management and as illustrated in cases below, rheumatologists may often be involved in helping diagnose and coordinate the patient pathway.
Case report -Case description: A 51-year old female ex-smoker experienced 6 months of fatigue, dry cough, mild exertional dyspnoea, sweats, mild weight loss and arthralgia after a cholecystectomy. She described lesions typical of erythema nodosum coinciding with a raised CRP (58g/L) which later normalised. Other than an elevated serum ACE (71 U/L), rest of testswere normal. Plain chest radiograph was normal but a co-incidental CT abdomen for non-specific abdominal discomfort showed small volume abdominal lymphadenopathy. Further imaging showed bilateral mediastinal and hilar lymphadenopathy. Pulmonary function tests and joint ultrasound were normal. EBUS sampling (August 2014) excluded malignancy but confirmed sarcoid granulomas. She briefly required non-steroidals for arthralgia. Four years later, she is still well with resolution of lymphadenopathy.
A 41-year old male non-smoker presented with 6 weeks of bilateral heel pain followed by myalgia, weight loss, headaches, sweats, intermittent blurred vision, and a non-specific neck rash. He was afebrile with normal urinalysis, CRPs 24-39 mg/L, CCP, ANCA, ANA negative, (Serum ACE sample insufficient). Infection screening (including TB) was negative. Slit lamp examination was normal. Trans-bronchial sampling of hilar lymphadenopathy seen on imaging excluded lymphoma but showed granulomas typical of sarcoidosis. The patient fully recovered within a few months without medication or recurrence.
A 63-year-old female was referred with ankle pain and swelling after 5 months of erythematous leg swelling treated initially as cellulitis. She also had bilateral, intermittent leg cramps and recent intermediate uveitis. She was positive for HLA B27 and ANA (homogenous speckled pattern) with a raised serum ACE (98 U). ANCA was negative, creatinine kinase normal. Background included treated squamous cell carcinoma and degenerative disc disease. Ankle problems had resolved when seen possibly due to prednisolone for uveitis. EBUS samplingof bilateral hilarlymphadenopathyconfirmedsarcoid histology. Since commencing azathioprine (50mg) for recurrent uveitis, shestayswell.
Case report -Discussion: Sarcoidosis is a granulomatous systemic disease thought to be Th-1 mediated but pathogenesis remains unclear. Heterogeneity in presentation and organ involvement may lead to delays or missed diagnoses. Like these cases, patients may have one or more presentations to variousmedical specialities before alink is made. Careful note of antecedent history, current symptoms and examination findings can point towards a differential of sarcoid particularly if bilateral ankle involvement or typical skin lesions are present. Erythema nodosum can occur which the first case had described. Given the smoking and weight loss history, the differential of malignancy had to be excluded first. Sarcoid arthropathy, as seen in these cases, typically presents as arthralgia, myalgia, or arthritis in either acute or chronic form. Sometimes myopathy and bone involvement are seen though erosive disease is uncommon. Cases often have minimal or no respiratory symptoms but chest imaging can pick up features including bilateral hilar lymphadenopathy (more than 75% of cases) and less commonly pulmonary parenchymal changes (nodules, groundglass changes, fibrosis) orpleural effusions. Most cases will resolve over time with minimal intervention as in the first two cases. Some require non-steroidal anti-inflammatories. Steroids may be required if there are more inflammatory features affecting joints or other organs. Disease modifying therapies (biologic and non-biologic) have been usedin more chronicor resistant cases. Sarcoid may co-exist with or mimic other conditions. In the last case, the unifying diagnosis of uveitis, skin changes and joint involvement seems to be sarcoid. However, it was interesting that the patient had mixed seroland showed some features of a seronegative arthritis profile as sponitis and sacroiliitis have been reportedwith sarcoidosis. logists are often familiar with features of the condition. Thus, can help link symptoms to guide appropriate investigations and furmanagement with good outcomes.
report -Key learningpoints coidosis can have a heterogeneous presentation so may take a for diagnosis to be made iratory symptoms may not be present despite findings on st imaging Rheumatologists are often involved in diagnosis and treatment when patients with sarcoid related arthralgia or arthritis type symptoms get referred . Most cases will resolve with minimal intervention . Early recognition can streamline investigations and management subsequently improving the patient journey . In cases with a mixed autoantibody profile, there may be a discussion on whether one or more conditions are present to explain all the features

EP18 TESTICULAR SARCOIDOSIS: A CHALLENGING DIAGNOSIS
Vishit Patel 1 , Sanketh Rampes 1 , Deepak Nagra 2 , Benjamin Clarke 2 and James Galloway 2 Case report -Introduction: Sarcoidosis is an inflammatory systemic disorder that is characterised by the formation of immune granulomas. Lung involvement is seen in about 90% of patients but extrapulmonary sarcoidosis can be a clinically challenging manifestation. Despite the majority remitting in three years, a considerable proportion (10-30%) develop chronic disease requiring continuous treatment. The development of extrapulmonary disease can be prior to, after or concomitant with pulmonary disease. Although cardiac, ophthalmic, neurological, and musculoskeletal manifestations have been described elsewhere, testicular involvement remains a rare phenotype of the disease which is poorly understood.
Case report -Case description: A 36-year old male patient born in Jamaica, presented in 2017 with unilateral left-sided testicular pain and enlargement measuring 20 x 16 x 18mm on ultrasound. This was initially suspected of malignancy or an atypical infection. A subsequent CT chest, abdomen and pelvis demonstrated nodal evidence of hilar, internal mammary and mediastinum involvement. Blood tests were unremarkable other than a raised lactate dehydrogenase (248 IU. mL (NR < 240)), low testosterone (5.2nmol/L (NR 10-30)) and androgen index (11.6 (NR 25-90). The patient underwent an orchidectomy and prosthesis, histological sampling demonstrated idiopathic granulomatous orchitis with features consistent of sarcoidosis. Malignancy could be excluded, and the absence of characteristic histochemical staining patterns favoured sarcoid to other differential diagnoses. He was efficaciously treated after a year's interval with prednisolone, which was gradually weaned from 40mg. However, eighteen months later, the patient returned complaining of right testicular pain. Ultrasound showed inflammation and enlargement of the testicle. PET-CT supported a recurrence of testicular involvement along with systemic disease involvement including neuropathy. His serum angiotensin-converting enzyme was raised at 118 IU/L (NR8-52) and responded similarly to high dose corticosteroid treatment. Additionally,