741 A complex clinical mosaic of severe autoimmune calcific constrictive pericarditis with striking haemodynamic response to immunosuppressive therapy

Autoimmune constrictive pericarditis constitutes a conundrum to modern cardiology with much uncertainty surrounding both pathophysiology and optimal treatment strategies. We hereby describe the case of a 35-year-old woman of Nigerian origin with severe right heart failure secondary to calcific constrictive pericarditis. Her past medical history included coagulation factor XI deficiency, leukopenia, 2nd trimester miscarriage and premature labour due to placenta previa with fibrin deposition. Further investigations revealed atrial fibrillation, severe biatrial enlargement, moderate tricuspid and mitral regurgitation, pericardial thickening, post-capillary pulmonary hypertension and right ventricular dip-and-plateau pattern, compatible with severe constrictive pericarditis. Extensive screening for infectious and autoimmune causes only revealed borderline positive ANA (1:80). Thereafter, the patient underwent complete surgical pericardiectomy with pericardial biopsies revealing fibrous thickening, diffuse calcification and lymphocyte/macrophage infiltrates, in the absence of giant multinucleated cells or granulomas. The patient was later discharged but soon experienced relapse of exertional dyspnoea presenting with right-sided haemo-pneumothorax (requiring pleural drainage), diffuse alveolar haemorrhage, large right-sided basal and infrascissural pleural effusion, and ascites. She was treated with high dose iv furosemide, oral ibuprofen and colchicine, suspension of rate control medications, achieving initial reduction in pulmonary oedema and ascites, relapsing however after attempts to switch to oral diuretic therapy. Due to the finding of persistent lymphopenia, further immunological tests were conducted, revealing raised IgG1 levels as well as altered peripheral lymphocyte populations (raised CD4+/CD8+ ratio and CD8+ central memory, reduced CD8 effector memory). This finding in conjunction with the history of factor XI deficiency, 2nd trimester miscarriage and placental fibrin deposition as well as the observation of painful cutaneous nodules at sites of venepuncture, suggestive of Koebner’s phenomenon, veered the diagnostic focus to a potential autoimmune aetiology and in particular to systemic lupus erythematosus (>10 ACR-EULAR score points with case reports describing all the above as potential disease manifestations). Furthermore, revision of thoracic CT scans, demonstrated bilateral migratory peribronchovascular nodules with ground-glass halo. CT- guided biopsies thereof were performed revealing focal alveolar damage with capillaritis and alveolar haemorrhage, further corroborating the clinical suspicion of autoimmune disease and justifying the introduction of high-dose oral corticosteroid therapy. In liaison with our tertiary rheumatology centre, the patient was later switched to mycophenolate with gradual weaning from corticosteroid. Concurrent cardiological follow-up revealed persistence of good haemodynamic status (NYHA class II, absence of pulmonary oedema and ascites) with oral diuretic therapy, regression of cutaneous symptoms and echocardiography demonstrating consistent reduction in both mitral and tricuspid regurgitation. This constitutes to our knowledge the first report of autoimmune calcific constrictive pericarditis with significant haemodynamic response to immunosuppressive therapy. Despite the relative rarity of this disease entity, early recognition and instatement of immunosuppressive treatment may prove fundamental to halt and potentially reverse the haemodynamic progression of this highly morbid condition.

Acute encephalitis in primary Sjögren’s syndrome: A case report and literature review

ABSTRACT Acute encephalitis is an extremely rare condition in primary Sjogren’s syndrome (pSS), and its characteristics and prognosis remain unclear. Here, we report the case of pSS presented with acute encephalitis. She was admitted to our hospital for acute disturbance of consciousness. Acute encephalitis was diagnosed based on the results of the cerebrospinal fluid test (the increase of leucocyte counts, proteins, and interleukin-6 levels), magnetic resonance imaging, and single-photon emission computed tomography with 99mTc. The infectious aetiologies and underlying malignancies were excluded. Serum anti-Sjogren’s syndrome-related antigen A autoantibody was positive with extremely high titre. The biopsy specimen of her labial salivary gland revealed a focal lymphocytic sialadenitis with a score of grade 4 in the Greenspan grade. She also developed diffuse alveolar haemorrhage during the clinical course. She was diagnosed with pSS complicated with acute encephalitis followed by diffuse alveolar haemorrhage and successfully treated with pulse steroids, high dose of prednisolone and intravenous cyclophosphamide. Our present case and literature review suggest that acute encephalitis associated with pSS can be treatable with the immunosuppressive therapy, and thus early recognition and treatment initiation are important for this life-threatening condition. Thus, pSS should be included in the differential diagnosis of unexplained encephalitis. Notably, our case characteristically showed diffuse alveolar haemorrhage, adding new insights into the pathogenesis of acute encephalitis associated with pSS that capillaritis might be the underlying cause of this condition.

Pathologically confirmed diffuse alveolar haemorrhage in lymphangioleiomyomatosis

A 40-year-old woman was referred to pulmonology after presenting with dyspnoea and self-limiting haemoptysis. Chest CT revealed diffuse ground glass opacities and small thin-walled cysts. Bronchoalveolar lavage cultures were negative and cytology revealed haemosiderin-laden macrophages. Transthoracic echocardiogram was normal. Connective tissue disease and vasculitis work-up were negative. Vascular endothelial growth factor-D level was indeterminate. Lung function was normal. She underwent video-assisted thoracoscopic lung biopsy. In addition to findings consistent with lymphangioleiomyomatosis, histopathological examination identified haemosiderosis without capillaritis, confirming a diagnosis of diffuse alveolar haemorrhage in the context of the associated clinical and radiographic features. Follow-up imaging after 5 months showed resolution of the diffuse ground glass opacities. Pharmacotherapy with sirolimus was not initiated due to absence of deterioration in pulmonary function. Diffuse alveolar haemorrhage in patients with lymphangioleiomyomatosis is a rare but important presentation. The few previously reported cases progressed to respiratory failure requiring mechanical ventilation.

Etanercept-Induced Anti-Glomerular Basement Membrane Disease

Anti-glomerular basement membrane (anti-GBM) disease is a rare form of small-vessel vasculitis that typically causes rapidly progressive glomerulonephritis with or without alveolar haemorrhage. Previously, there has only been one reported case of tumour necrosis factor-α (TNF-α) antagonist-induced anti-GBM disease. Here, we describe the first reported case of etanercept-induced anti-GBM disease. A 55-year-old Caucasian man was referred to our tertiary specialist renal centre with a history of painless macroscopic haematuria. The patient has been receiving weekly etanercept injections over the past 12 months for psoriatic arthropathy. The serum immunology panel results highlighted a significantly raised anti-GBM titre (370.1 U). Etanercept was stopped, and the patient was empirically commenced on pulsed methylprednisolone, cyclophosphamide, and plasma exchange. A renal biopsy showed crescentic glomerulonephritis. Few days after admission, he tested positive for coronavirus disease 2019 (COVID-19), and a decision was made to withhold cyclophosphamide. There was further decline in renal function with hyperkalaemia for which he received 2 sessions of haemodialysis. He was restarted on cyclophosphamide upon discharge. The patient was switched to rituximab treatment afterwards as he developed leucopenia 2 weeks following the commencement of cyclophosphamide. The serum creatinine level continued to improve and remained dialysis-independent. In conclusion, with the increased use of etanercept and other TNF-α antagonists, the prescribing clinician must be aware of the rare but life-threatening drug-induced vasculitis. We recommend careful monitoring of renal indices with the use of this class of medications.

Case Report: Cyclophosphamide in COVID-19 – when an absolute contraindication is an absolute necessity

Background: Despite many studies on COVID-19, our knowledge of it remains incomplete. In some cases, treating SARS-CoV-2 infection concomitant with other diseases can be particularly challenging, as finding an appropriate treatment may involve some risks. Case presentation: A 34-year-old SARS-CoV-2 positive patient admitted due to fever, dyspnoea, haemoptysis and pneumonia, developed alveolar haemorrhage and acute kidney injury. Due to his severe state, abnormalities in laboratory tests and rapidly progressing loss of kidney function, kidney biopsy, as well as antibody panel were carried out, in which perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) were found with a high titer (>200; N: <1:20). The results of kidney biopsy, combined with clinical manifestation and laboratory findings prompted the diagnosis of rapidly progressing glomerulonephritis (RPGN) in the course of p-ANCA vasculitis. Initial treatment consisted of heamodialyses, remdesivir, plasmaphereses, intravenous immunoglobulins, antibiotics, corticosteroids and fraxiparine. Once the haemorrhage had subsided, kidney function had been partially retrieved and heamodialyses had no longer been necessary, cyclophosphamide treatment was initiated, despite being contraindicated in COVID-19 according to its summary of product characteristics. Immunotherapy is still continued. The patient has already received a total of 2.4g of cyclophosphamide (4 cycles of 600mg each every three weeks). Pulmonary and radiological regression, as well as improvement of renal parameters have been achieved. Conclusions: We suspect that cyclophosphamide, the drug of choice in p-ANCA vasculitis, could be a potential factor providing regression of the radiological changes in the lungs and it could have prevented the patient from developing acute respiratory distress syndrome. COVID-19 diagnosis should not exclude searching for other diseases which can have a similar course. When treating a patient in a life-threatening condition, a departure from trying to find the perfect timing of cyclophosphamide delivery should be considered, as delaying it could cause potentially greater harm.

Diffuse alveolar haemorrhage: a rare complication of clopidogrel use

Diffuse alveolar haemorrhage (DAH) has been reported as a rare complication of clopidogrel use and is usually a diagnosis of exclusion. We describe the case of an 88-year-old Native American woman who presented with acute hypoxic respiratory failure with CT scan of the chest showing diffuse bilateral ground-glass opacities. She had been on clopidogrel for 6 months for a carotid artery stent. Bronchoscopy with bronchoalveolar lavage and transbronchial biopsies revealed DAH. Infectious and autoimmune work-up were all negative. Clopidogrel was stopped and high-dose steroids were started. Her symptoms gradually improved until she was discharged from the hospital. The differential DAH is broad. Anticoagulant-induced DAH should be part of the differential diagnosis, and is usually a diagnosis of exclusion.

Diffuse alveolar haemorrhage and myocardial infarction: life-threatening effects from self-injected hyaluronic acid dermal filler

Hyaluronic acid (HA) is a widely used dermal filler for soft tissue augmentation. We described a case of a 38-year-old transwoman who presented with sudden onset of severe respiratory distress following self-injection of HA dermal filler. She developed multiple episodes of pulmonary haemorrhage, and her chest X-ray showed diffuse ground-glass opacities consistent with diffuse alveolar haemorrhage (DAH). There were no relevant drugs or past medical histories. Anti-nuclear antibodies and rheumatoid factor were negative. Initially, the pulmonary haemorrhage episodes and ventilation requirement improved with systemic steroid, however she subsequently developed acute myocardial infarction with progressive clinical deterioration leading to death. To the best of our knowledge, this is the first HA-related DAH with myocardial infarction reported with a fatal outcome. This case highlights the importance of awareness and the necessity of having a high suspicion of DAH in patients with history of illicit HA dermal filler use.