EP03 Parechovirus in a pathologist

Abstract Case report - Introduction A 42-year-old pathologist presented with a 1-week history of muscle pain and subjective weakness. CK level on 2 occasions was >3000. The patient was systemically well with no past medical history, medication, or foreign travel. He had 1-day history of shivering with no recorded pyrexia. He reported pain in his proximal muscles and neck and subjective muscle weakness and lack of finger dexterity with no objective findings. Case report - Case description Autoantibody panel and inflammatory markers were performed which were normal. Full blood count with differential white cell count including eosinophils was normal. There was a modest rise in transaminases. Myositis panel was negative. Full viral screen was positive for parechovirus with titre of 30 on several samples. MRI proximal musculature showed increased fluid signal in the perifascial region of both thighs primarily involving the hamstrings, not definitive for myositis but suggestive of fasciitis. Case report - Discussion Parechovirus is a picornavirus, often causing mild gastrointestinal or respiratory illness but has been associated with epidemic myalgia and myositis during outbreaks of parechovirus in a Japanese population. The patient improved spontaneously with CK reduced to 187 and improved symptoms after 1 week. We expect a good outcome and will review on patient's request if necessary. Case report - Key learning points Parechovirus can cause myofasciitis which is usually mild and self-limiting. It can be associated with elevated CK, transaminases and MRI findings and can be confirmed on respiratory viral swab.

Investigations revealed a normal full blood count and CRP<1 with normal liver and renal function tests. Her urinalysis was unremarkable. Immunology was negative for ANA, ANCA and rheumatoid factor. Immunoglobulins were normal. Two weeks later her symptoms were fully resolved. Case report -Discussion: Coronaviruses are single-stranded RNA viruses with nearly 30 strains recognised to infect humans. They induce both an innate and adaptive immune system response. It is hypothesised that a dysregulated innate system response, leading to a prolonged adaptive response triggers damaging inflammation and a potential cytokine storm. This is associated with poor outcome during primary viral infection. Variations in this immune response, with different underlying HLA genotypes could lead to other post infectious immune mediated phenomena, such as Paediatric Multisystem Inflammatory Syndrome -Temporally associated with COVID-19. There is a European registry collating data about patients with known rheumatic diseases who are admitted with COVID-19. There is emerging data regarding Paediatric Inflammatory Multisystem Syndrome -Temporally associated with SARS-CoV-2 (PIMS-TS). There is a growing suggestion that a subgroup of patients is developing a COVID-19 associated post viral fatigue syndrome. We suggest that a registry to collect information on de novo autoimmune diseases presenting post COVID-19 isalso commenced. Case report -Key learning points: COVID-19 infection is associated with a wide variety of sequalae, including rheumatological ones. Classic post viral Reactive arthritis has been seen. A registry to collect information on de novo autoimmune presentations would be highly informative. : A 31-year-old female doctor was gofherlips,dysphagia,andawidespreadurtishe had a one-week history of fever, cough, of malaise and weight loss. Her symptoms had started at the end of April 2020 during the peak of the COVID-19 pandemic in the United Kingdom. Three days later she developed painful swelling of her wrists, elbows, knees, and hands. She reported no back or sacroiliac joint pain, enthesitis or any previous history of inflammatory joint pains. She had a history of platelet dysfunction and was treated with Desmopressin. Clinical examination revealed a widespread urticarial rash over her face, limbs, and trunk, with no nail abnormalities. She had active synovitis in her right wrist, elbow, and mild bilateral knee effusions. All other joints including spine and sacroiliac joints were normal. She had no dactylitis or enthesitis. Systemic examination was normal. Investigations revealed Hb 113 g/L, MCV 88.2 fL, Platelets 282 x 10 9 /L, WCC 6.6 x 10 9 /L and Lymphocytes of 0.63 x10 9 /Lwith normal neutrophil and eosinophil count. CRP was raised at 107mg/L. She had a negative autoimmune screen including ANA, ANCA, IgM-RF, anti-CCP antibodies and HLA B27. Plain radiographsofknees were normal.SARSCoV-2PCRwas positive following a nasal swab. Urine and blood cultures were negative. Treatment was commenced with intravenous hydrocortisone and antihistamines with resolution of her angioedema symptoms; however, her rash and arthritis persisted. The patient was diagnosed with Reactive Arthritis (ReA), urticarial rash and angioedema secondary to COVID-19 infection. Prednisolone 30mg daily was started, and within a week her arthritis and rash markedly improved. Prednisolone was tapered over six weeks. By her two-month clinic follow up, she reported no further joint swelling and was functioning normally. Case report -Discussion: The most common complication of COVID-19 isAcuteRespiratoryDistressSyndrome(ARDS)however several other serious complications have been identified including cardiac injury, thromboembolic events, neurological abnormalities, and an aggravated inflammatory response causing a cytokine storm. ReA is a post infectious arthritis commonly seen following gastrointestinal or genitourinary infections and is yet to be recognised as a complication of this disease. ReA most commonly presents as an asymmetrical peripheral or axial spondyloarthropathy. The affected joints do not contain pathogen. More than half of ReA cases resolve spontaneously within six months without requiring long-term treatments. Up to 20% of patients with COVID-19 infection have been shown to develop cutaneous manifestations including erythematous rash, vesicular rash, acral ischaemia, rash with petechiae, and widespread urticaria. This has led to the recent addition of rashes to the World Health Organisation (WHO) Criteria for diagnosis of COVID-19 infection. Additionally, as COVID-19 has an incubation period of 14 days where patients can be asymptomatic, cutaneous manifestations may serve as an early indicatorof infection, aiding ina more rapid diagnosis. Case report -Key learningpoints: We present a rare case of ReA secondary to COVID-19 infection, with complete resolution of symptoms following administration of oral glucocorticoids. A detailed history and examination of the musculoskeletal system should be undertaken in all patients presenting with COVID-19. Urticarial rashes should be considered as an early symptom of COVID-19 infection as per the WHO criteria for diagnosis. Glucocorticoids can be considered in treating patients with this presentation, where traditional anti-inflammatory agents have been refractoryor contraindicated.

Claire Masih, Michael Dologhan and Andrew Cairns Musgrave Park Hospital, Belfast, United Kingdom
Case report -Introduction: A 42-year-old pathologist presented with a 1-week history of muscle pain and subjective weakness. CK level on 2 occasionswas >3000. The patient was systemically well with no past medical history, medication, or foreign travel. He had 1-day history of shivering with no recorded pyrexia. He reported pain in his proximal muscles and neck and subjective muscle weakness and lack of finger dexterity with no objective findings.
Case report -Case description: Autoantibody panel and inflammatory markers were performed which were normal. Full blood count with differential white cell count including eosinophils was normal. There was a modest rise in transaminases. Myositis panel was negative. Full viral screen was positive for parechovirus with titre of 30 on several samples. MRIproximalmusculatureshowed increased fluid signal in the perifascial region of both thighs primarily involving the hamstrings, not definitive for myositis but suggestiveof fasciitis. Case report -Discussion: Parechovirus is a picornavirus, often causing mild gastrointestinal or respiratory illness but has been associated with epidemic myalgia and myositis during outbreaks of parechovirus in a Japanese population. The patient improved spontaneously with CK reduced to 187 and improved symptoms after 1 week. We expect a good outcome and will review onpatient's request ifnecessary. Case report -Key learning points: Parechovirus can cause myofasciitis which is usually mild and self-limiting. It can be associated with elevated CK, transaminases and MRI findings and can be confirmed on respiratory viral swab. Case report -Introduction: This is a case of Pakistani female with limited systemic sclerosis and associated mild interstitial lung disease. The lung disease was complicated by SARS-COV-2 related pneumonitis in April 2020 and thatledto treatment challenges. She was previously seen in multiple private hospitals and labelled as Rheumatoid arthritis. She was being treated with long term steroids and Methotrexate. After her initial presentation to our Rheumatology services, her diagnosis was correctly revised to Systemic Sclerosis with phenotype of CREST. Her treatment was adjusted to Vasodilators and Mycophenolate due to skin and Lung involvement. Case report -Case description: This is a case of 40-year-old Pakistani female who had been having multiple joint pains since 2010. She also experienced severe Raynaud's. She presented to our Rheumatology clinic in December 2018. Her symptoms included recurrent digital ulcers, tight and tough skin at fingers and Raynaud's worse during winter months. Her examination confirmed peripheral cyanosis with multiple digital ulcers with superimposed infection, marked sclerodactyly and calcinosis. She was started on Vasodilator therapy including calcium channel blocker and PDE5 inhibitor due to severity of ulceration. Infection was managed with prolonged course of antimicrobial therapy. Her immunology showed positive anti nRNP/Sm. Anti-centromere and anti Scl 70 were negative. Her condition fit description of CREST (Calcinosis, RP, Oesophageal dysmotility, telangiectasia). Her management included weaning off Methotrexate and reductionin the dose of corticosteroids. In February 2019, Respiratory work up showed normal Chest radiograph, High resolution CT chest showing no significant abnormality and FEV1 82%, FVC 86%, and DLCO 77%. Her PASP was 25mmHg. Overall, her condition remained stable over the course of next year. Her medication included Cellcept, low dose prednisolone, hydroxychloroquine, and Sildenafil. More importantly, Digital ulcers have been well controlled with combined vasodilatortherapy. In April 2020, she developed SARS-CoV-2 with mild respiratory symptoms and was admitted to a different hospital. Fortunately, she responded well to ward based supportive and symptomatic treatment with no need for respiratory support. Subsequently, she has seen a different respiratory physician and had repeat imaging of chest which has led todilemma whether thegroundglassopacitiesinboth lungsis duetoscleroderma lung or COVID-19 related lung disease. She was given high dose prednisolone by the respiratory physician which has been reduced in rheumatology clinic. The new findings on chest imaging are sequelae of SARS-COV-2. Case report -Discussion: This case highlights few important points as below: Systemic sclerosis diagnosis was not made for many years even though she has had severe digital ulcers for a long time. She was being managed as Rheumatoid arthritis. Systemic sclerosis remains a difficult disease to diagnose and is still under recognised. SARS-COV-2 related illness has not affected this patient adversely despite the fact of being on long term maintenance prednisolone of 7.5mg daily dose and Cellcept 2gm. Her cellcept was temporarily stopped during acute illness. We know that viral pneumonitis can present with typical ground glass opacities in bilateral areas of lungs and differential diagnosis does include connective tissue related lung disease but this lady had no significant respiratory involvement prior to COVID-19 illness and follow up scan will help to decide if this is disease progression or related to viral cause. Case report -Key learning points: There are multiple learning points in this case: Continuity of care under same primary team can avoid confusion related to diagnosis and diagnosis related complications. This lady had none, or mild subclinical lung involvement related to systemic sclerosis prior to contracting COVID-19 illness. Her CT chest findings after the episode of SARS-COV-2 were attributed to systemic sclerosis as she was seen by different respiratory team. This continuity is not always possible, but MDT collaboration needs to be improved across hospitals and across various departments. Systemic sclerosis remains an under diagnosed and under recognized complex rheumatic disorder and more primary care physicians need to be educated so they can appropriately refer these cases to Rheumatology services. Multi-disciplinary collaboration between Rheumatology, Respiratory and other specialties is the key point to manage these complex cases. This case also highlights an interesting observation that presence of significant immune disorder and immunosuppressant medication does not always equate to worse outcome if patient contracts SARS-COV-2. Supportive care, appropriate observation, and temporary suspension of DMARD in such cases can avoid any further complications.

Great Western Hospital NHS Foundation Trust, Swindon, United Kingdom
Case report -Introduction: COVID-19, the infectious disease caused by the novel coronavirus SARS-CoV-2, and first described in Wuhan, China in December 2019, has affected more than 19 million patients worldwide and resulted in more than 700,000 deaths at the time of writing 1 . Patients with rheumatic diseases and those receiving immunosuppressive treatment are felt to be at greater risk of complications from this illness, though registry and trial data should help refine our understanding of these risks. We hereby describe a case of COVID-19 complicating an unusual rheumatic illness, resulting in severe multi-system disease and premature death. Case report -Case description: A 69 year-old male presented to rheumatology and haematology with symmetrical polyarthritis, thrombocytopenia (18 x 10 9 /L), eosinophilia (25.4 x 10 9 /L), raised C-reactive protein (CRP, 43 mg/L), positive rheumatoid factor (>200), antinuclear antibody (ANA) and anti-Ro. Bone marrow biopsy did not demonstrate evidence of haematological malignancy. Seropositive rheumatoid arthritis and connective tissue disease overlap were diagnosed, and treatment with Prednisolone 60mg daily was initiated. Despite rituximab and intravenous immunoglobulins, thrombocytopenia deteriorated on reducing corticosteroids, however the addition of mycophenolate mofetil (MMF) allowed gradual prednisolone tapering to 3mg daily. Hydroxychloroquine was briefly added but discontinued due to headaches. MMF was discontinued after he developed fungal pneumonia followed by jaundice. Liver biopsy was consistent with druginduced cholestasis, attributed to co-amoxiclav, and his liver function tests (LFTs) improved on ursodeoxycholic acid. Following a further deterioration in thrombocytopenia, hyperferritinaemia and new onset erythema nodosum, he had a repeat bone marrow examination. This demonstrated large areas of fibrosis and granulomatous inflammation with a dense, pleomorphic T-cell infiltrate, but no haemophagocytosis.
Haematologists felt this was reactive and prednisolone dose was increasedto 10mg daily. Six months later he developed cholangitis. Magnetic resonance cholangiopancreatography (MRCP) demonstrated a tight 4cm stricture of the distal common bileduct(CBD)within the headof pancreas,whichwas diffusely swollen without any clear focal mass. Serum amylase was mildly elevated (316 units/L). Concurrent CT thorax, abdomen and pelvis demonstrated bilateral ground-glass changes within the lungs, and a SARS-CoV-2 nasopharyngeal PCR test was positive, though he had no respiratory symptoms or oxygen requirementat that stage. Sadly, fourdays after the CT scan and before aplanned endoscopicretrograde cholangiopancreatography (ERCP) could be performed, he became markedly hypoxic with plain chest x-ray features suggestive of COVID-19 pneumonia. Despite medical management, including doubling of his prednisolone dose, herapidly deteriorated and died.