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Still's disease in children (systemic juvenile idiopathic arthritis - JIA) and adult Still's disease (ASD) are considered as systemic autoinflammatory diseases of unknown etiology, which are based on similar immunopathogenetic mechanisms associated with genetically determined disorders of the mechanisms of innate immunity. ASD was first described 50 years ago by the English rheumatologist Eric George Lapthorne Bywaters. The molecular basis of ASD immunopathogenesis is the activation of innate immunity associated with NLRP3 inflammasome-dependent mechanisms of inflammation, characterized by the overproduction of "pro-inflammatory" cytokines - interleukin (IL) 1 and IL-18, inducing the synthesis of other proinflammatory inflammatory mediators. A review of new data concerning the mechanisms of immunopathology, clinical polymorphism, laboratory biomarkers and the possibilities of ASD pharmacotherapy is presented. Particular attention is paid to the prospects for the use of monoclonal antibodies to IL-1beta - canakinumab. The problems associated with the generality of clinical and laboratory disorders, pathogenetic mechanisms and pharmacotherapy of ASD and coronavirus disease 2019 (COVID-19) are considered.Copyright © 2021 Authors. All rights reserved.
ABSTRACT
Still's disease in children (systemic juvenile idiopathic arthritis - JIA) and adult Still's disease (ASD) are considered as systemic autoinflammatory diseases of unknown etiology, which are based on similar immunopathogenetic mechanisms associated with genetically determined disorders of the mechanisms of innate immunity. ASD was first described 50 years ago by the English rheumatologist Eric George Lapthorne Bywaters. The molecular basis of ASD immunopathogenesis is the activation of innate immunity associated with NLRP3 inflammasome-dependent mechanisms of inflammation, characterized by the overproduction of "pro-inflammatory" cytokines - interleukin (IL) 1 and IL-18, inducing the synthesis of other proinflammatory inflammatory mediators. A review of new data concerning the mechanisms of immunopathology, clinical polymorphism, laboratory biomarkers and the possibilities of ASD pharmacotherapy is presented. Particular attention is paid to the prospects for the use of monoclonal antibodies to IL-1beta - canakinumab. The problems associated with the generality of clinical and laboratory disorders, pathogenetic mechanisms and pharmacotherapy of ASD and coronavirus disease 2019 (COVID-19) are considered.Copyright © 2021 Authors. All rights reserved.
ABSTRACT
Background: A 54-year- old male presented to our centre with a chronic non-productive cough and breathlessness. Recent history of COVID treated and resolved few months back. He had a history of brain surgery performed five years back but details not known. Physical examination revealed no oedema and bilateral coarse creps with bronchiolar breathing. Laboratory findings indicated neutrophilic leucocytosis, elevated inflammatory markers, with elevated troponin I and D dimers. Urine analysis suggested microscopic haematuria with sediments. While 24 hour quantification revealed sub nephrotic proteinuria. As auto immune workup and vasculitis profile was negative and patient has not improved in spite of standard of therapy hence we went ahead with CT-Chest indicating ground-glass opacities in bilateral lung parenchyma and prominent interlobular/intralobular septal thickening. Then Bronchoscopy done which revealed the blood-stained secretions in the main stem bronchi and diffuse alveolar haemorrhage in bilateral bronchial segments indicating an inflammatory study, while tuberculosis diagnostic panel and infective bio fire panel in BAL was negative. Meanwhile, his repeat BAL culture suggested Carbapenem resistant Acinetobacter baumannii complex infection. As the patient did not respond to the standard of care for vasculitis. Probability considered was a small vessel vasculitis (namely Granulomatous polyangiitis) was considered due to lung manifestation involving upper respiratory tract with epistaxis, neutrophilic leucocytosis, elevated acute reactive protein, and renal manifestation including microscopic haematuria and proteinuria. However he responded poorly to conventional standard of treatment including pulse steroids and IVIG. Hence after MDT discussion we proceeded with lung biopsy which showed linear cores of lung tissue infiltrated by a malignant neoplasm and acinar pattern suggesting Invasive mucinous adenocarcinoma. Hence we went ahead with the biopsy diagnosis for the treatment plan. As he was to be started on chemotherapy, but he suddenly collapsed and went into hypotension, bradycardia, and cardiac arrest. In spite of high supports and post 4 cycles of CPR, was unable to revive and sadly succumbed to his illness. Discussion(s): In this rare case, the original diagnosis pointed to the pulmonary-renal syndrome, an autoimmune disease characterized by diffuse pulmonary haemorrhage and glomerulonephritis. However, negative autoimmune antibodies and vasculitis profile along with lung biopsy results indicated an unusual case of malignant lung adenocarcinoma presented with pulmonary renal syndrome. Conclusion(s): In cases suggesting pulmonary-renal syndromes, if autoimmune work up is negative and response is suboptimal relook the diagnosis.
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SESSION TITLE: Critical Systemic Disease Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Granulomatosis with polyangiitis(GPA) is an autoimmune small vessel vasculitis that is included in the group of anti-neutrophilic cytoplasmic antibody(ANCA)- associated small vessel vasculitides (AAVs). GPA is a systemic disease, however acronym ELK is used to describe the most common involvement of Ear, nose, throat, Lungs, and Kidneys. We report a case of GPA, highlighting its presentation. CASE PRESENTATION: 59-year old female presented with vaginal bleeding, malaise, blurry vision, non productive cough and shortness of breath few days after receiving COVID-19 vaccine. Physical exam was remarkable for bilateral conjunctival injection with right sided ptosis and inguinal lymphadenopathy. Laboratory findings were significant for acute kidney injury and anemia. Computed tomography (CT) of chest revealed bilateral bronchovascular nodules and masses with interlobular septal thickening and enlarged mediastinal lymph nodes. Fine needle aspiration of left inguinal lymph node was negative for malignancy. Bronchoscopy with bronchial brush revealed alveolar hemorrhage with capillaritis;bronchoalveolar lavage(BAL) showed hemosiderin laden macrophages. Tissue biopsy was negative for malignancy. Testing for pulmonary renal syndrome was positive for C-ANCA and proteinase-3 (PR-3) antibodies. Anti-GBM antibody and anti-MPO antibody was negative. Plasmapheresis (PLEX) and pulse dose steroids were initiated however the patient was unable to tolerate the treatment. Her clinical condition continued to decline requiring multiple pressors, broad spectrum antibiotics and continuous renal replacement therapy. She was transitioned to comfort care per family's wishes and passed away. DISCUSSION: GPA is a rare necrotizing granulomatous vasculitis of small to medium sized vessels that can affect any organ but mainly involves the upper and lower respiratory tract. Necrotizing glomerulonephritis is common. Pulmonary involvement can include consolidation, tracheal or subglottic stenosis, diffuse alveolar hemorrhage, pleural effusion and interstitial lung disease. Lymphadenopathy, as seen in our patient is a rare presentation. Tissue biopsy is crucial for the diagnosis. Association with PR-3 ANCA is seen in more than 80% of GPA patients. Cases of AAVs after administration of COVID vaccine have been reported in the literature, although it is difficult to demonstrate causal relationship. Treatment of GPA with immunosuppression, usually corticosteroids, rituximab or cyclophosphamide, is recommended. The role of PLEX continues to evolve with emerging data, but use of this therapy is reasonable for patients with severe kidney injury and DAH secondary to active vasculitis refractory to immunosuppressive therapy. CONCLUSIONS: Early diagnosis of GPA is challenging as it can mimic metastatic lung malignancy. It should be considered in a broad range of differentials when evaluating patients presenting with pulmonary nodules. Reference #1: Greco A, Marinelli C, Fusconi M, Macri GF, Gallo A, De Virgilio A, Zambetti G, de Vincentiis M. Clinic manifestations in granulomatosis with polyangiitis. Int J Immunopathol Pharmacol. 2016 Jun;29(2):151-9. doi: 10.1177/0394632015617063. Epub 2015 Dec 18. PMID: 26684637;PMCID: PMC5806708. Reference #2: Kitching, A. R., Anders, H. J., Basu, N., Brouwer, E., Gordon, J., Jayne, D. R., Kullman, J., Lyons, P. A., Merkel, P. A., Savage, C., Specks, U., & Kain, R. (2020). ANCA-associated vasculitis. Nature reviews. Disease primers, 6(1), 71. https://doi.org/10.1038/s41572-020-0204-y Reference #3: Szymanowska-Narloch, A., Gawryluk, D., Błasińska-Przerwa, K., & Siemińska, A. (2019). Atypical manifestations of granulomatosis with polyangiitis: the diagnostic challenge for pulmonologists. Advances in respiratory medicine, 87(6), 244–253. https://doi.org/10.5603/ARM.2019.0062 DISCLOSURES: No relevant relationships by Sean Davidson No relevant relationships by Eric Flenaugh No relevant relationships by Marilyn Foreman No relevant relationships by KOMAL KAUR No relevant relationships by Gabriela Oprea-Ilies
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A 48 y.o. male maintenance worker in a rat-infested building with history of tobacco and marijuana smoking, atrial fibrillation on no medications was admitted in July 2021 for fever, headache and body aches for 5 days and new onset of hemoptysis. Initial labs notable for BUN 36 mg/dl, Cr 1.4 mg/dl urine protein 100 mg/dl RBCs 5-10/hpf, platelets 46,000. total bilirubin 3.8 mg/dl direct bilirubin 3.0 SARS-CoV-PCR negative and CXR revealed patchy bilateral infiltrates. He was intubated on day 2 and had ventricular fibrillation and cardiac arrest on day 3 with rapid return of purposeful movement. He had worsening anemia and thrombocytopenia, positive ANA and dsDNA, leading to use of steroids and plasmapheresis on Day 6 when peak bun/cr was 91/3.1 with urine protein/cr ratio 0.7, urine microscopy 2 rbc/hpf, urine Na 20 meq/l, urine osm 775 mosm/kg and cpk 400 U/l. These tests were negative or normal: Anti-GBM, ANCA, repeat ANA, repeat dsDNA, C3, C4, HIV, RF, hepatitis C RNA, cryoglobulins, ASO titer, ADAMTS13, Pneumocystis PCR, Sputum AFB, blood, AFB and fungal cultures, viral and fungal testing, hanta virus antibodies. Leptospira antibodies IgM by Dot Blot were positive and Leptospirosis diagnosis confirmed by NYC Department of Health (DOH) after obtaining confirmatory microscopic agglutination testing from the CDC. Urine and blood Leptospira DNA PCR not detected. He remained intubated with FiO2 requirement at 100% prior to his death on hospital day 16. Initially pulmonary renal syndrome considered but he was later found to have pre-renal azotemia. The elevated bilirubin led to testing for leptospirosis, his final diagnosis. In September 2021 the NYC DOH reported 14 cases of leptospirosis (increased from 5 cases in 2020), 13 of which had acute renal and hepatic failure, with 2 having severe lung involvement (1). This case is the only one in this group who died. The leptospirosis case fatality rate for severe diffuse alveolar hemorrhage exceeds 50%. Early appropriate antibiotic treatment prior to lab confirmation has been recommended by the CDC and may decrease severity of disease.
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Introduction: Double-positive vasculitis with anti-polynuclear cytoplasm (ANCA) and anti-glomerular basement membrane (GBM) antibodies is a rare entity of systemic vasculitis defined by the presence of ANCA and anti-GBM antibodies. Methods: We report a rare case of pulmonary-renal syndrome with atypical clinical presentation. Results: A 52 year-old smoking man with a history of exposure to hydrocarbons and uretheral lithiasis, presented in April 2021 epigastralgia and vomiting. the investigations concluded to H.pylori gastritis and ulcer and he received a quadruple therapy. The kidney function was correct in April 2021. The evolution was marked by the persistence of symptoms and urine output had decreased for a few days. He was found to have renal dysfunction (serum creatinine: 2000 µmol/L). Abdominal CT scan without iodinated contrast injection showed severe hydronephrosis of the right pelvicalyceal system with cortical thinning and dilatation of the right ureter. The two kidneys had regular outlines seat multiple bilateral renal cysts with exophytic development. He had a nephrosomy with secondarily a right double-J stent with slight improvement of renal function. The patient presented then with acute respiratory distress.Testing for COVID-19: PCR and serology were negatives. Chest CT scan showed alveolar syndromeevoking pulmonary overload. No pneumopathy covid was shown. The evolution was marked by the non improvement by depletion and he developed hemoptic sputum and low-abundance epistaxis. The attitude was non-invasive ventilation and broad-spectrum antibiotics therapy. Control chest CT showed emphysematous lung with signs of fibrosis with bilateral subpleural nodules. A rereading of the scanner showed intraalveolar hemorrhage which has regressed on the imaging of the control. Based on these data, pneumo renal syndrome was suspected and a bronchoscopy was performed showing alveolar hemorrhage with 70% siderophageswith Gold score superior to 100. Anti-GBM and p-ANCA and antibodies were positive at a high titer. Electroneuromyogram was without anomaly. Kidney biopsy was not done because of the presence of multiple cysts. The patient received pulse methylprednisone for three days followed by oral prednisone and underwent eleven sessions of plasmapheresis. Intraveinous Cyclophosphamide has been started. He showed remarkable recovery as his lung fields cleared with negativity of GBM antibodies. Kidney function didn't improved and he remained dependent on dialysis. Conclusions: Our observation is exceptional since the clinical and radiological presentation of the patient was not that of a pulmonary-renal syndrome. The elements of this syndrome have in fact been masked by the obstacle on the urinary tract on one hand and the hypothesis of a covid19 pneumonia on the other hand in the face of the epidemiological context. Atypical feature of pulmonary renal syndrome should be kept in mind to avoid diagnostic and treatment delays. No conflict of interest