UNUSUAL CASE OF ANTI-SYNTHETASE SYNDROME CORRELATED WITH EXPOSURE TO COVID-19 INFECTION OR VACCINE

SESSION TITLE: Systemic Disease with Diffuse Lung Symptoms Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Since its first detection at Wuhan, China, SARS-CoV-2 (novel coronavirus 2019) has engulfed the world with more than 100 million cases and manifestations of COVID19 have been evolving over time. Various post COVID19 syndromes are being recognized. Reactive arthritis, connective tissue disorders such as myositis and pulmonary complications have been correlated with exposure to COVID infection. We describe the case of antisynthetase syndrome in a patient correlated with exposure to COVID infection or vaccine. CASE PRESENTATION: A 68 year old female with history of hypertension and exposure to COVID infection in the family member, presented with 2-3 months worsening generalized body ache/pain started 2 weeks after receiving second dose of mRNA vaccine. Patient also reported dyspnea and leg swelling for 1 month. Upon presentation, she was placed on 4 liter oxygen via nasal cannula. Chest x-ray concerning for infiltrates, possibly COVID. CT chest no pulmonary embolism but evidence of pneumonia superimposed on chronic appearing bronchiectasis. Flu and Covid testing were negative. Patient was started on IV antibiotics for community acquired pneumonia. Labs showed elevated ESR, CRP and CK level. No fever, weakness, mechanics hands, rash or Raynaud's phenomenon. Infectious work up remained negative. No lymphadenopathy on CT chest to suggest sarcoid. ACE level normal. ANA and anti aminoacyl-tRNA synthetase antibody positive but other ENA were negative. HMG-COA ab negative. MPO/PR3 neg. Echocardiogram was unremarkable. Work up was suggestive of Anti synthetase syndrome with interstitial lung disease(ILD), a form of dermatomyositis. Patient was started on intravenous steroid with good improvement in symptoms and later transitioned to oral prednisone. Patient was discharged on minimal home oxygen with plan to start immunosuppressive medications. DISCUSSION: We are unsure if our patient had COVID19 infection since COVID testings were negative (antigen, antibody and nucleic acid detection ). The likelihood of autoimmune and rheumatic diseases in COVID19 survivors is a big issue. COVID19 infection may unmask previously undiagnosed rheumatic conditions and precipitate de novo disease, both of which may persist after resolution of the initial infection. Corticosteroids remain the cornerstone of early treatment with initial doses at 1mg/kg of the ideal body weight. In an effort to reduce steroid related side effects, other immunosuppressive agents should be considered at the outset of therapy, particularly when treating anti-synthetase syndrome with manifestations of ILD. CONCLUSIONS: Patients with anti-synthetase syndrome with ILD could have correlation with exposure to COVID infection or vaccination, and are steroid responsive. It is likely that clinical improvement may result from prompt suppression of inflammatory systemic response by corticosteroid. Reference #1: 1. Ahmed S, Zimba O, Gasparyan AY. COVID-19 and the clinical course of rheumatic manifestations. Clin Rheumatol. 2021;40(7):2611-2619. doi:10.1007/s10067-021-05691-x Reference #2: 2. Witt LJ, Curran JJ, Strek ME. The Diagnosis and Treatment of Antisynthetase Syndrome. Clin Pulm Med. 2016;23(5):218-226. doi:10.1097/CPM.0000000000000171 DISCLOSURES: No relevant relationships by ELINA MOMIN No relevant relationships by Mohammedumer Nagori

Acute urticaria to chlorhexidine -the first case reported from our practice

Background: Chlorhexidine is one of the most commonly diagnosed causes of perioperative anaphylaxis. However, the spectrum of symptoms of Chlorhexidine allergy is wide which can result in its neglecting as a potential causal agent. What is more, publications from some countries like Bulgaria, are still limited, even lacking. Our aim was to present the first case of perioperative chlorhexidine allergy diagnosed in one of the largest Bulgarian tertiary university hospitals. Case presentation: A 54-year old man was referred to the Allergy Unit of the tertiary hospital St. George Plovdiv for evaluation and subsequent elective surgery procedure. Two months ago during a previous surgery in an outpatient clinic, the patient experienced generalized urticaria 30 min after the procedure's start. When taking the medical history, patient reported repeated itchy hand rash after regularly using disinfectant solution after the beginning of COVID-19 pandemic. However, these symptoms had been neglected. The use of chlorhexidine-containing solution for preoperative skin preparation was detected in the record from the previous surgery as well as in the disinfectant label. Upon patient's evaluation, skin prick test with perioperative drugs, including chlorhexidine (0.5%) was carried out. Allergy to chlorhexidine was diagnosed. All chlorhexidinecontaining products were avoided and elective surgery procedure was performed successfully. Chlorhexidine allergy card was provided and detailed further instructions were given to the patient. Conclusions: This is the first reported case of allergy to Chlorhexidine, diagnosed in one of the largest tertiary Bulgarian hospital. The presented case highlights the importance of awareness and identification of minor reactions to chlorhexidine. A relevant clinical history is essential and in our case, it directed the investigation to the culprit agent. On suspicion of allergy, patients should be referred for allergist consultation, preferably in a centre with experience in perioperative allergy investigation.

Adult onset PIMS-TS with secondary haemophagocytic lymphistiocytosis: Into the eye of the cytokine storm

Case report-IntroductionA small sub-group of COVID-19 patients develop secondary haemophagocytic lymphohistiocytosis (sHLH), a multisystem progressive hyperinflammatory syndrome characterised by fever, hepatosplenomegaly, hyperferritinaemia, cytopenia, and multiple-organ failure, which if not identified and promptly treated may be fatal. There have been isolated reports of adults developing PIMS-TS, a rare inflammatory multisystem syndrome seen in children with COVID-19 which shares common features with Kawasaki disease, toxic shock syndrome and macrophage activation syndrome/sHLH. Here we present a case of COVID-19-associated PIMS-TS in an adult complicated by frank sHLH (COV-HLH) which, after a protracted course, responded to combination immunotherapy including the IL-1 antagonist anakinra.Case report-Case descriptionA 22-year-old female of Nigerian-descent with sickle cell trait presented with fever, headache, sore throat, arthralgia, abdominal pain, diarrhoea/vomiting, swollen feet/legs, and macular rash on hands/forearms. A 3-day flu-like illness occurred 8 weeks earlier. Persistent pyrexia, tachycardia and hypotension required ICU admission for inotropic support. Although she briefly required oxygen, hypoxaemia was not a prominent feature. Bloods revealed CRP>200mg/L, ferritin<14,000ng/mL, raised D-Dimer, procalcitonin, Troponin-T and ALT, anaemia, lymphopenia, and neutrophilia. Computed-tomography showed mild bibasilar subpleural ground-glass changes, pelvic free fluid, and peritoneal enhancement. As treatment for suspected COV-HLH, or connective tissue disorder, intra-venous hydrocortisone 100mg QDS was given;fever resolved and blood parameters transiently improved. Second nasopharyngeal SARS-CoV-2 RT-PCR was positive and screen for other infection and autoimmune disease negative. Echocardiography and CTA excluded coronary aneurysms although Troponin-T peak was 330ng/L.Rapidly rising ferritin and triglycerides, falling cell counts and fibrinogen, led to a diagnosis of COV-HLH. Intra-venous anakinra 70mg (1mg/kg) BD was initiated. When pyrexia remained >40 °C, inotrope requirement persisted, cell counts fell and ferritin rose to 45,861ng/ml, anakinra was increased over 48h to 200mg BD with intra-venous methylprednisolone 1g OD x2. After 7 days anakinra was weaned to 100mg subcutaneous BD enabling discharge. Outpatient bone marrow aspirate/trephine showed reactive hyperplasia, no leukaemia or haemophagocytosis. Genomic testing showed no primary genetic cause. A week later she was readmitted with fatigue, arthralgia, pyrexia, tachycardia, haematuria, and ferritin of 23,000ng/mL (nadir 4,000ng/mL). FDG-PET showed hepatosplenomegaly with no lymphoma. Anakinra was increased to 200mg IV BD with IVIG 1mg/kg OD x2 and methylprednisolone 1g IV OD x3, then cyclosporine 1mg/kg IV BD. Fevers and haemoproteinuria resolved within 1 week and inflammatory markers fell allowing discharge on a reducing regime of subcutaneous anakinra, oral prednisolone and cyclosporine. She remained well;ferritin and FBC finally normalised >2 months after presentation.Case report-DiscussionThrough the UK HLH across speciality collaboration (HASC) we are aware of only a handful of UK cases of adult presentation PIMS-TS and even fewer with frank sHLH. Our patient's ethnic background and presentation were typical for paediatric PIMS-TS. Hence, we actively excluded coronary artery aneurysms, a key feature of the Kawasaki-type variant of PIMS-TS.Initial COVID-19 swabs were negative as was extensive investigation for other sepsis triggers. A high clinical suspicion of COVID-19 led to the second positive swab and early recognition of sHLH. Diagnosis of HLH can be challenging due to its non-specific features and was even more difficult in critically ill patients during the peak of the pandemic, where bone marrow biopsy and cross-sectional imaging (key components of diagnostic scoring systems such as the HScore) were difficult to obtain. Persistent pyrexia, hyperferritinaemia and recognition of worsening trends in all relevant domains raised suspic on of sHLH. On initiation of anakinra, her HScore was only 118, although her illness peak was 162, well above the HASC agreed threshold of 132 for HLH diagnosis during the pandemic. She subsequently had a negative bone marrow biopsy in line with >50% of critical care patients with sHLH;a demonstration that biopsy proven haemophagocytosis is not necessary for a clinical diagnosis of sHLH. No other sHLH trigger was found.Early recognition and intensive treatment may have contributed to the positive outcome;sHLH mortality in ICU patients can reach nearly 70%. These decisions were facilitated by early discussion with MDT members of HASC. The initial dose of 70mg IV BD and speed of wean after an effective dose was achieved were insufficient. A longer period on 400mg anakinra daily, a slower wean, plus addition of methylprednisolone, IVIG and cyclosporin appeared to aid the resolution of her relapse. Case report-Key learning points COVID-19 infection is complicated by hyperinflammatory syndromes (cytokine storm, PIMS-TS, sHLH) in a significant minority of patients. In the absence of a treatment for COVID-19, early recognition of treatable complications should be a clinical priority.Adult clinicians should be aware of PIMS-TS which may rarely occur in young adults, especially those of African descent. The CDC definition extends to those aged up to 21. Cardiac aneurysms should be actively excluded in this group.The challenges associated with sHLH diagnosis became more apparent during the peak of the COVID-19 pandemic where key tests were difficult to obtain. Current scoring systems are insensitive for evolving sHLH. A high index of clinical suspicion and a multidisciplinary team approach, in which rheumatologists are key, is important for early recognition and treatment. Although no other sHLH trigger was found in this case, we have seen COV-HLH patients with underlying connective tissue disorder, haematological malignancy or a primary genetic defect, which should be considered if COV-HLH patients do not respond to treatment.Optimal treatment for sHLH and the hyperinflammatory syndromes associated with COVID-19 is not supported by randomised controlled trials but there is accumulating evidence for anakinra. Whilst its use in sHLH remains off-license, UK guidelines have been developed, with an emphasis on early and high dose treatment. Careful anakinra weaning regimens should be considered and patient progress regularly reviewed to avoid relapse of sHLH and subsequent readmission. Our patient also appeared to have a favourable response to corticosteroid and other combined immunosuppressive treatments including IVIG and cyclosporine. It remains to be seen if the incidence of adult-onset PIMS-TS and COV-HLH will reduce now that Dexamethasone is standard of care in adult patients with COVID-19.