COVID-19 IN A PATIENT WITH GRANULOMATOSIS WITH POLYANGIITIS: MANAGEMENT TACTICS

Patients with ANCA-associated vasculitis (AAV) cause extreme alertness during the coronavirus disease 2019 (COVID-19) pandemic, associated with many factors: the initial damage to the respiratory system (upper respiratory tract, lungs) and kidneys, immunosuppressive treatments, difficult prognosis of COVID-19 with the risk of AAV exacerbation. We present a clinical case of a moderate COVID-19 in a patient with granulomatosis with polyangiitis, who received anti-B cell therapy with rituximab (RTX) for a long time. Coronavirus pneumonia developed one year after RTX, while B-lymphocyte depletion persisted. In order to achieve an adequate antiviral immune response and prevent hyperinflammation, treatment was carried out with antiviral drugs, anticoagulants, convalescent plasma, human normal immunoglobulin, and interleukin-6 antagonist tocilizumab. Possible predictors of severe COVID-19 in patients with AAV are discussed.Copyright © 2023 Ima-Press Publishing House. All rights reserved.

COVID-19 IN A PATIENT WITH GRANULOMATOSIS WITH POLYANGIITIS: MANAGEMENT TACTICS.

Patients with ANCA-associated vasculitis (AAV) cause extreme alertness during the coronavirus disease 2019 (COVID-19) pandemic, associated with many factors: the initial damage to the respiratory system (upper respiratory tract, lungs) and kidneys, immunosuppressive treatments, difficult prognosis of COVID-19 with the risk of AAV exacerbation. We present a clinical case of a moderate COVID-19 in a patient with granulomatosis with polyangiitis, who received anti-B cell therapy with rituximab (RTX) for a long time. Coronavirus pneumonia developed one year after RTX, while B-lymphocyte depletion persisted. In order to achieve an adequate antiviral immune response and prevent hyperinflammation, treatment was carried out with antiviral drugs, anticoagulants, convalescent plasma, human normal immunoglobulin, and interleukin-6 antagonist tocilizumab. Possible predictors of severe COVID-19 in patients with AAV are discussed.Copyright © 2023 Ima-Press Publishing House. All rights reserved.

An unusual presentation of malignant Invasive Mucinous Adenocarcinoma of Lung mimicking Pulmonary Renal syndrome

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.

New onset unusual Wegener's granulomatosis associated with COVID-19: a case report

Background: Granulomatosis with polyangiitis (GPA) or Wegener's granulomatosis is an autoimmune disorder with a wide spectrum of manifestations that mostly primarily presents with respiratory symptoms such as cough, dyspnea, and hemoptysis and leads to a high mortality rate if left untreated. It is a relatively uncommon condition, characterized by necrotizing granulomatous vasculitis of small-and medium-sized vessels. Recent studies have shown that hyperactivation of immune cells in patients with the coronavirus disease 2019 (COVID-19) leads to elevated levels of various autoantibodies and inflammatory cytokines including interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). There are the same factors that involve in the pathogenesis of autoimmune diseases such as GPA.Case presentation: While there have been several reported cases of COVID-19 occurring in patients receiving immunosuppressant treatment for GPA, here we report a case of a 72-year-old woman with a history of coronavirus disease 2019 (COVID-19) who suddenly suffered unilateral vision and hearing loss and peripheral facial palsy on the same side. Chest computed tomography (CT) demonstrated a subpleural consolidation in the inferior lobe of the left lung. Based on the radiology report, chest CT evidence was due to a history of COVID-19 pneumonia. CT scans of the paranasal sinus showed pansinusitis and necrosis of the nasal septum. According to the available evidence, mucormycosis was clinically suspected, and the patient underwent endoscopic sinus surgery. Eventually, the histopathological analysis revealed a diagnosis of Wegener's granulomatosis.Conclusions: Since GPA and its complications can be prevented only through strong clinical suspicion and early diagnosis, our presentation of this case aims to increase awareness of autoimmune diseases in COVID-19 patients even after recovery.

GRANULOMATOSIS POLYANGIITIS MASQUERADING AS COVID-19: A DIAGNOSTIC DILEMMA DURING THE PANDEMIC

SESSION TITLE: Pulmonary Manifestations of Systemic Disease Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Granulomatous polyangiitis (GPA), previously known as Wegener's granulomatosis, is a rare syndrome characterized by inflammation of small and medium sized vessels. The clinical presentation can be very heterogenous and differentiation from an infectious disease can be challenging initially. Here, we present a case of a young male presenting with respiratory symptoms during the pandemic, presumed to have coronavirus disease 2019 (COVID-19) though after extensive workup was later diagnosed with GPA. CASE PRESENTATION: A 19-year-old male presented to the emergency department (ED) with complaints of low-grade fever and dry cough for one week. He reported having abdominal pain, fatigue, loss of appetite and polyarthralgia. An outpatient upper gastrointestinal endoscopy revealed gastritis and duodenitis. In the ED, his vitals included a temperature of 101.8°F, blood pressure of 115/65mmHg, heart rate of 99/min, respiratory rate of 18/minute and oxygen saturation of 99% on room air. COVID-19 testing was negative. A computerized tomography of the chest revealed extensive ground glass opacities. He was presumptively diagnosed with COVID-19 and started on dexamethasone therapy along with azithromycin for atypical pneumonia. However multiple tests for SARS-CoV-2 were negative. Another consideration was COVID-19 induced multisystem inflammatory syndrome given the patients young age. Infectious workup included negative testing for human immunodeficiency virus, Legionella, tick borne diseases and mycoplasma. As febrile episodes continued, he developed microcytic anemia, microscopic hematuria, and petechial rash on his ankles. Antinuclear antigen screen was negative, but C-antineutrophil cytoplasmic and anti-proteinase-3 antibodies were positive. Renal biopsy revealed GPA. He was prescribed pulse dose steroids and transitioned to immunotherapy. DISCUSSION: GPA is a challenging diagnosis given multiple system involvement, though early identification and initiation of treatment are important to prevent long term sequalae. In our case, acute onset febrile illness and pulmonary ground glass opacities led to repeated COVID-19 testing potentially delaying the diagnosis. Ultimately, the correct diagnosis was made and confirmed on renal biopsy. We believe our case highlight the importance of keeping a broad differential and considering vasculitis in these situations for prompt diagnosis. CONCLUSIONS: GPA can often mimic respiratory infectious processes, a high index of suspicion is necessary for timely diagnosis. Reference #1: Selvaraj V, Moustafa A, Dapaah-Afriyie K, et alCOVID-19-induced granulomatosis with polyangiitis. BMJ Case Reports CP 2021;14:e242142 Reference #2: Qurratulain, Q., Ahmed, A., & Jones, Q. (2021). Lesson of the month: Severe granulomatosis with polyangiitis (GPA): a diagnostic challenge during the COVID-19 pandemic. Clinical Medicine, 21(1), 79. DISCLOSURES: No relevant relationships by Aamna Khan No relevant relationships by Usama Sadiq No relevant relationships by Rehan Saeed

A CASE OF GRANULOMATOSIS WITH POLYANGIITIS

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

RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS IN THE SETTING OF GRANULOMATOSIS WITH POLYANGIITIS AND COVID-19

SESSION TITLE: COVID-Related Critical Care Cases SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm INTRODUCTION: We present a case of rapidly progressive glomerulonephritis in a patient with granulomatosis with polyangiitis and COVID-19 pneumonia. CASE PRESENTATION: A 72 year old man presented to the hospital with shortness of breath, fatigue, fevers, and malaise. Chest x-ray showed bilateral lower lobe infiltrates consistent with COVID-19 pneumonia and creatinine of 1.57, elevated from baseline of 1.30. He was diagnosed with COVID-19 pneumonia and admitted to the Intensive Care Unit due to acute hypoxic respiratory failure and worsening acute kidney injury. Past medical history was significant for granulomatosis with polyangiitis (GPA) with recurrent deep venous thromboses and splenic infarct. Warfarin was held due to supratherapeutic INR on admission. COVID-19 drug therapy was initiated, including baricitinib, remdesivir and decadron. Creatinine began to rise significantly and renal ultrasound was ordered but showed no hydronephrosis or acute abnormality of the kidneys. There was no improvement with administration of fluids, and hemodialysis was initiated due to worsening creatinine with a peak of 12.09 and a strong suspicion for rapidly progressive glomerulonephritis (RPGN) in the setting of GPA. High-dose steroid therapy was started and daily hemodialysis was continued. Patient required transfer to a tertiary care center for multifactorial shock where he continued to receive dialysis therapy. Patient eventually required mechanical ventilation and ultimately expired. DISCUSSION: GPA is an autoimmune small and medium vessel vasculitis most often associated with anti-neutrophil cytoplasmic antibodies (c-ANCA). Without treatment, GPA has a high mortality rate due to systemic vasculitis. Treatment of GPA includes immunosuppressive therapies like rituximab or cyclophosphamide. Environmental and infectious processes are thought to cause GPA. Viruses have also been shown to cause GPA with two such cases documented with SARS-CoV-2. Our case illustrates a patient with known previously GPA who developed RPGN in the setting of COVID-19. RPGN can lead to rapid loss of renal function in GPA and can be the initial presentation of the disease process. However, care must be taken as often the presentation of GPA lung sequela may mimic those of COVID-19, including dyspnea, hemoptysis, and radiographic changes. Obtaining ANCA autoantibodies as well as a urinalysis showing proteinuria can help distinguish GPA and guide clinical judgment in starting high-dose steroid therapy early in renal failure due to RPGN in the setting of COVID-19. CONCLUSIONS: COVID-19 in patients with GPA can trigger renal failure due to RPGN. Reference #1: Bressler MY, Pathak N, Cervellione K, et al. New Onset Granulomatosis with Polyangiitis Associated with COVID-19. Case Rep Dermatol Med. 2021. Reference #2: Hasan MR, Sakibuzzaman M, Tabassum T, Moosa SA. A Case of Granulomatosis with Polyangiitis (Wegener's Granulomatosis) Presenting with Rapidly Progressive Glomerulonephritis. Cureus. 2019. Reference #3: Lutalo PM, D'Cruz DP. Diagnosis and classification of granulomatosis with polyangiitis (aka Wegener's granulomatosis). J Autoimmun. 2014. DISCLOSURES: No relevant relationships by Kristin Davis No relevant relationships by Charles Peng

COVID-19 in RITUXIMAB TREATED PATIENTS with INFLAMMATORY RHEUMATIC DISEASES

Background: At the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) pandemic, the influence of anti-infammatory therapy on the course of SARS-CoV-2 infection in patients with infammatory rheumatic diseases (IRD) was unknown. In the meantime, several data indicate an association of severe courses of COVID-19 with the use of ritux-imab (RTX). Objectives: To gather further knowledge about SARS-CoV-2 infections in RTX-treated IRD patients, data from the German COVID-19-IRD-registry were analysed. Methods: Hospitalisation was used as a surrogate of COVID-19 severity. Baseline characteristics, disease features, medication and outcome of COVID-19 were compared in RTX-treated inpatients and outpatients. Results: In total, 3592 cases were reported in the registry, which included 130 RTX patients (3.6%) for our analysis. RTX-treated inpatients were older than RTX-treated outpatients (median age 63 y vs 56 y, p=0.007). Patients with granulomatosis with polyangiitis treated with RTX (n=32) showed a significant higher COVID-19 related hospitalisation rate (33% vs 11%, p=0.005), which was not the case for patients with rheumatoid arthritis (49% vs 50%). Cardiovascular comorbidities were reported more frequently in hospitalised RTX-treated patients (20% vs. 6%, p=0.032). More than 50% of the RTX-treated inpatients developed COVID-19 related complications, e.g. acute respiratory distress syndrome. The median time period between the last RTX treatment and SARS-CoV-2 infection was shorter in inpatients than in non-hospitalised patients (3 (range 0-17) vs. 4 months (range-29), p=0.039). The COVID-19 related mortality rate was 14% (n=19) in RTX-treated IRD patients. In RTX-treated inpatients and outpatients, there were no relevant differences with respect to the use of concomitant glucocor-ticoids or other disease modifying anti-rheumatic drugs, disease activity, median last RTX dose or median number of immunomodulatory drugs prior to RTX treatment. Conclusion: In addition to general risk factors, such as age and comorbidities, it is already known that IRD patients treated with RTX show a higher rate of severe COVID-19. In our registry, RTX-treated patients with granulomatosis with polyangiitis appear to be at even higher risk to develop severe COVID-19 compared to other IRD. Moreover, the shorter the time since the last RTX treatment, the higher seems to be the risk of developing severe COVID-19. This might be explained by a more profound B-cell depletion in the frst weeks after RTX treatment warranting further studies.

LATE-ONSET NEUTROPENIA after RITUXIMAB TREATMENT in PATIENTS with ANCA-ASSOCIATED SYSTEMIC VASCULITIS: A RETROSPECTIVE ANALYSIS of A REGISTER-BASED PATIENT COHORT

Background: Anti-B-cell therapy with rituximab (RTX) plays an important role in the induction and maintenance therapy of ANCA-associated vasculitis (AAV). Late-onset neutropenia (LON) has been reported following RTX therapy. Objectives: Based on a retrospective analysis of the register of AAV patients (pts) treated with RTX, to study the incidence and outcomes of LON. Methods: 140 AAV pts (median age 52 (20-83) years, 57% women) were treated with RTX between 2009 to 2021: 63 with granulomatosis with polyangiitis (GPA), 45 microscopic polyangiitis (MPA), 24 eosinophilic granulomatosis with polyangi-itis (EGPA), and 8 unclassifed AAV. The median total dose of RTX was 3.5 (0.5-45) g. As a rule, single 500-mg infusions were used with an interval of 4-6 months for retreatment courses. The duration of follow-up exceeded 6 months after the frst dose of RTX. Regular pts monitoring every 3 months included estimation absolute neutrophil count (ANC). LON was defned as unexplained neutropenia occurring 3 weeks after the last RTX infusion. Results: LON I-IV grade was noted in 16 (11.4%) AAV pts: 6 GPA, 4 MPA, EGPA, and 2 unclassifed AAV. In 7 out of 16 cases (43.7%) LON developed after the frst course of RTX. Neutropenia grade I was observed in 3 pts (ANC 1.68-2.0x109/l, 2-15.5 months after the last RTX infusion), grade II-in 4 patients (1.1-1.5x109/l, 3-9 months after RTX). Neutropenia grade I-II resolved independently, without adverse reactions. LON grade IV was noted in 9 pts (0.06-0.3x109/l, 1.1-11 months after RTX), 3 of them received leukopoie-sis-stimulating drugs with normalization of ANC. In one EGPA pt febrile LON grade IV developed twice (in 2017, 11 months after RTX;in 2019, 4 months after RTX and complicated by uterine bleeding). Fatal outcome occurred in out of 16 cases (31.2%): 1 MPA, 3 GPA, and 1 EGPA. In 3 fatal cases LON was complicated by pneumonia (in 2 with septic shock), in one with acute myocardial infarction and another one with progression of chronic renal failure. According to our registry, the total mortality among 140 AAV pts receiving RTX was 11.4%, while 5 of 16 fatal cases (31.2%) had LON grade IV. Three of the 5 death were noted in 2013-2014, which attributed to the use of cyclophos-phamide >2 gm before RTX, as well as insufficient awareness of the risk of LON, which contributed to the delay in control of a full blood count, untimely diagnosis of LON and late treatment. At the beginning, the original drug Mab-thera was used, while after 2014 biosimilar Acellbia was mainly used. The disadvantages of this study: the lack of information about the ANC in 4 cases with COVID-19 and fatal outcome. Conclusion: LON after RTX therapy can develop in 11.4% of AAV pts, which exceeds the data for rheumatoid arthritis (1,3-3%) [1,2]. Our register data are lower than the rate of LON in AAV, presented by D. Tesfa et al. (23%) [1], which could be affected by the use of low-dose RTX for retreatment courses. LON accounts for a signifcant part in the structure of deaths of AAV pts (31.2%). It needs to careful monitoring of ANC in pts receiving RTX and awareness of both pts and physicians about the risk of LON.

COVID-19 course in granulomatosis with polyangiitis: single center experience with review of the literature.

BACKGROUND: Coronavirus disease 2019 (COVID-19) shares some clinical features with new-onset granulomatosis with polyangiitis (GPA) or GPA flare that may lead to a challenge in differential diagnosis. To date, little is known whether GPA can be induced by COVID-19. Herein, we aimed to seek the frequency and mortality rates of COVID-19 in our GPA cohort, and along with the literature cases, to evaluate clinical features and treatments of GPA patients with COVID-19. We also tried to identify clinical features of COVID-19 induced GPA. METHODS: As of July 2021, we conducted a systematic literature review using different spelling combinations of "COVID-19 and GPA" in the PUBMED database. In total, 18 cases were found in the literature, 6 of them had COVID-19 induced GPA. The remaining 12 of literature cases and 6 cases in our GPA cohort (n = 81) had a COVID-19 infection while followed-up with GPA. We grouped these 18 patients as GPA+COVID-19. RESULTS: The frequency of COVID-19 was 7.4% in GPA cohort and mortality rate was 33% in GPA patients with COVID-19. The most common symptoms of GPA+COVID-19 patients were fever, cough, arthralgia/myalgia, and malaise. The most frequent treatments for GPA before the COVID-19 infection were steroids (72%) and rituximab (56%). Three patients who received rituximab also had COVID-19 reinfection. In the literature cases, mortality was observed in 4 (22%) of 18 patients with GPA+COVID-19. The most common symptoms of COVID-19 induced GPA were dyspnea, fever and cough. DISCUSSION: In our GPA cohort, we observed a higher mortality rate compared to global WHO data. In patients followed up with GPA, rituximab treatment may be precarious for both COVID-19 disease and reinfection. Our study also provided some clues about the diagnostic challenge of GPA induced by COVID-19.

DON'T LOSE SIGHT OF GPA

CASE: A 48-year-old female with no medical history presented with 2 days of decreased vision in the right eye. She reported painless blurry vision that progressed to near complete vision loss. The vision loss was accompanied by one month of progressively worsening cough, body aches, and subjective fevers. She denied smoking and reported no sick contacts. Physical exam was notable for submandibular lymphadenopathy, bilateral conjunctival injection, and grossly decreased vision of the right eye. She also endorsed decreased sensation in bilateral lower extremities distally. Her initial labs showed leukocytosis (13), thrombocytosis (754), and elevated inflammatory markers (ESR 105 and CPR 359). A chest CT showed bilateral upper lobe consolidations and scattered mass like opacities bilaterally. Ophthalmic exam of the right eye revealed multiple small retinal infarctions consistent with paracentral acute middle maculopathy. A CT head was negative and TTE showed no vegetation. Additional testing revealed negative TB, COVID, and normal complements. Initial ANCA testing was negative, however a repeat test was strongly positive for ANCA with PR3 significantly elevated to 428. She was diagnosed with granulomatosis with polyangiitis (GPA) vasculitis and treated with prednisone and started induction therapy of Rituximab. IMPACT/DISCUSSION: GPA is a small-medium vessel necrotizing vasculitis and the most common anti-neutrophil- cytoplasmic-antibody (ANCA) associated vasculitis. GPA classically involves the upper respiratory tract, lungs, and kidneys referenced by the ELK criteria (ENT, Lung, Kidney) commonly used for diagnosis. ENT findings are present in 70-100% of cases with the nasal cavity and paranasal sinuses most commonly involved. Roughly 50% have pulmonary involvement on presentation, as in this patient, while only 10-20% have initial renal involvement. A prodrome of systemic symptoms including body aches and fevers is often present. GPA is closely associated with c-ANCA, with autoantibodies to proteinase 3 (PR3) positive in over 80% of cases. This patient did have prodromal symptoms yet her primary presenting symptom of vision loss was atypical. Eye involvement is not part of the diagnostic triad yet it can occur in GPA. When it does present, it usually manifests as scleritis, conjunctivitis, or uveitis. Retinal infarctions, as seen in this patient, are uncommon and make this case an atypical presentation of GPA. Additionally, ANCA positivity is related to disease activity and a negative ANCA should not exclude GPA from a differential. Not all patients will be ANCA positive on initial presentation and 10% of patients with GPA will remain ANCA negative. CONCLUSION: Providers should consider atypical presentations of GPA in addition to the classic triad of ENT, Lungs, and Kidneys. Renal manifestations are often missing initially and involvement of other systems, such as ocular, can take place. With a positive c-ANCA and high clinical suspicion, treatment should not be delayed.

Diagnosis and treatment of vasculitis

Primary angiitis of the central nervous system (PACNS) is an inflammatory disease affecting exclusively small and medium-sized vessels of the central nervous system. CNSvasculitis may also occur in systemic diseases like giant cell arteritis, Takayasu arteritis, granulomatosis with polyangiitis, or Behçet syndrome. The most common presenting symptoms of CNS vasculitis are multifocal symptoms associated with recurrent episodes of ischemia or hemorrhage, encephalopathy-related cognitive and affective abnormalities, and headaches. Diagnostic work up of CNS vasculitis includes MRI, CSF examination, digital subtraction angiography and brain biopsy. High-resolution, contrast-enhanced, compensated and fat-saturated MRI imaging of the cerebral vessel walls (black-blood imaging) may be of some value for the detection of CNS-vasculitis. Patients with normal CSF findings are unlikely to have CNS vasculitis. Brain biopsy should be performed in suspected PACNS. Important differential diagnoses include reversible cerebral vasoconstriction syndrome, moyamoya angiopathy and infectious vasculopathies (VZV, SarsCoV2, borreliosis, bacterial endocarditis). The adherence to diagnostic criteria and the avoidance of inappropriate therapies are essential. Treatment recommendations for CNS-vasculitis include glucocorticoids in combination with cyclophosphamide or rituximab;however, randomized clinical trials of PACNS treatment do not exist. Induction therapy is recommended for 6 to 12 months. After remission is achieved, treatment may be continued with substances as mycophenolate mofetil, methotrexate, or azathioprine. Repeated clinical, CSF- and neuroradiological monitoring is needed to determine the individual duration of maintenance therapy.

Tracheobronchopathia Osteochondro-What? A Rare Disorder of the Airway

Airway abnormalities may be due to a multitude of conditions. Symptoms do not occur until there is very significant narrowing, and therefore these conditions are often incidentally found. It is important to consider a broad differential.This case is a 47 year old woman with history of mild intermittent asthma and chronic sinusitis who presented to the emergency department with four weeks of malaise, shortness of breath, cough, and two days of hemoptysis. On CT imaging she was found to have tracheal wall thickening, calcifications and projections along the trachea, as well as extensive right upper and middle lobe, and lingular ground glass opacities as seen in figure 1. With hindsight, similar tracheal abnormalities were noted on chest x-ray in 2019. During admission, ENT was consulted and she was noted to have saddle nose deformity. Nasal biopsy was performed and revealed evidence of chronic inflammation, but no other abnormalities. Extensive workup was performed including rheumatologic workup with mildly positive ANA, mildly elevated ESR and CRP, negative ANCAs, MPO, PR3, RF. Bronchoscopy was pursued and direct visualization of nodules were noted along the anterior and lateral aspects of the trachea, as well as narrowing of the right upper lobe segmental bronchi, also seen in figure 1. Bronchoalveolar lavage cultures revealed Citrobacter freundii complex, Group G beta hemolytic streptococcus, Providencia rettgeri, Enterococcus avium, Pseudomonas aeruginosa, Klebsiella pneumoniae, in addition to rhinovirus and COVID-19. Biopsy was not performed due to patient intolerance of the procedure and desaturation. Ultimately, the pulmonary infiltrates were felt to be a separate process from the tracheal nodules. She improved clinically, and was discharged on antibiotic therapy with a plan for close outpatient follow up.Tracheobronchopathia osteochondroplastica (TO) is a rare condition. Imaging is often the first clue, as symptoms come late in disease course. The differential diagnosis of imaging findings consistent with TO include relapsing polychondritis, granulomatosis with polyangiitis, amyloidosis, along with a host of others. Diagnosis of TO often requires multidisciplinary involvement to evaluate other etiologies,and ultimately bronchoscopy for direct visualization. (Table Presented).

Granulomatosis With Polyangiitis Presenting as Complete Hearing Loss.

Granulomatosis with Polyangiitis is a rare autoimmune vasculitis that is classically characterized by effects on the upper respiratory tract, lungs, and kidneys. Delay in diagnosis is often attributed to variable and sequential presentation of symptoms rather than concurrent symptomatology. It is important to recognize the wide range of initial presenting symptoms as early diagnosis and treatment is critical in preventing potentially irreversible damage resulting from delayed diagnosis. We present a case of a 29-year-old male with history of mixed sensorineural-conductive hearing loss presumed to be secondary to chronic otitis media who presented to the emergency department with complaint of hematemesis with a subsequent diagnosis of granulomatosis with polyangiitis.

A case report of granulomatosis with polyangiitis in a middle aged women

Background: Wegener's granulomatosis (Granulomatosis with polyangiitis) is a rare systemic autoimmune disease of unknown etiology characterised by triad of necrotising granulomatous inflammation of upper and lower respiratory tract, glomerulonephritis, and disseminated vasculitis. Case Study: A 50 year old female presented with complaints of running nose since last 8 months. Patient also had low grade fever, generalised body pain, productive cough, shortness of breath on exertion, pedal oedema for last 2 months. She had an 2-3 episodes of blood in sputum 15 days back. On examination saddle nose found. HRCT chest shows multiple cavitating nodules with consolidation. Lab findings shows raised ESR, CRP, COVID RT PCR negative and positive C-ANCA (Anti neutrophilic cytoplasmic antibody), red blood cell casts, and albumin present in urine. Sputum for AFB negative. Patient discharged on corticosteroids and cyclophosphamide and advised for regular follow up. Discussion: Wegener's granulomatosis is an antineutrophilic cytoplasmic antibody associated small vessel vasculitis. Prevalence of this disease varies from 3/1,00,000 to 16/1,00,000. Typically this involve the lungs and kidneys. It can be of generalised severe form or localised limited form. Our patient clinical course, CT findings and his strongly positive C-ANCA were considered diagnostic of wegener's granulomatosis. Treatment include corticosteroids and immunosuppressants. Conclusion: The early diagnosis and prompt treatment of multisystem disorder is necessary to prevent complication such as diffuse alveolar haemorrhage CT is the imaging modality of choice for diagnosis, surveillance and follow up in patients with wegener's granulomatosis.

Gentle Giant: An Unusual Cause of Heart Block

Introduction: Inflammatory cardiomyopathies can be a diagnostic dilemma. Early management can lead to reduced morbidity and mortality for patients. We describe a rare presentation of an unusual cardiomyopathy. Case Report: A 58-year-old female presented with a 10-day prodrome of cough, NYHA class III dyspnea, and fatigue with minimal symptoms of orthopnea, paroxysmal nocturnal dyspnea or peripheral edema. She was previously healthy with no cardiac medications. Family history was significant for granulomatosis with polyangiitis. COVID-19 swab was negative. She was symptomatic with transient complete heart block and junctional escape of 20bpm. A temporary transvenous pacemaker was placed. Echocardiogram showed biventricular dysfunction with left ventricular ejection fraction < 30%. Troponin and brain-natriuretic peptide were elevated. Coronary angiogram showed no significant occlusions. CT excluded pulmonary embolism, pneumonia, or adenopathy. She was initiated on heart failure medications but beta blocker was not started given heart block. Six days into admission, her heart failure improved but she developed transient complete heart block without junctional escape. There was no ventricular ectopy. Evaluation for rheumatologic, infectious, and inflammatory causes showed elevated C-reactive protein and antineutrophil cytoplasmic antibodies. The remainder of the workup was negative. Leading diagnoses were idiopathic giant cell myocarditis or cardiac sarcoidosis. An endomyocardial biopsy revealed multinucleated giant cells and myocyte necrosis. She was diagnosed with giant cell myocarditis. Prior to discharge, she had defibrillator insertion and was initiated on prednisone and tacrolimus. Shortly after this time, she returned with critical cardiogenic shock despite intensification of immunosuppressive therapies and was listed for cardiac transplant. Giant cell myocarditis (GCM) is a rare and often fatal autoimmune cause of heart failure. Patients frequently present with congestive heart failure, ventricular arrhythmia and a rapid progression of symptoms. In GCM, it is rare to present with atrioventricular conduction delays. Given the crossover in symptoms with sarcoidosis and GCM, diagnosis may be challenging. In this case of an acute presentation of heart failure and complete heart block, endomyocardial biopsy was central to the diagnosis and management of GCM.

A Case of Antineutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis Post COVID-19 Vaccination.

In this report, we examine the case of a patient who developed antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis after receiving the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine. This is a case of a 62-year-old female who received the first dose of COVID-19 vaccine in July 2021 before presenting a few weeks later with migrating polyarthralgia and hemoptysis. Autoimmune workup was positive for ANCA against proteinase 3 (PR3).

Acute Respiratory Distress Syndrome During the COVID-19 Era

During the current pandemic, the 2019 novel coronavirus (SARS-CoV-2) has quickly moved to the top of the list of potential causes of acute respiratory distress syndrome (ARDS) in patients presenting to the hospital. Potential COVID-19 infections should continue to be quickly identified and treated when indicated, but it is important that we not forget about the other potential causes of ARDS. In this case series, we will discuss 3 cases of ARDS that were passed off as likely SARS-CoV-2 infections but were all discovered to be negative for COVID-19. This highlights the importance of maintaining a thorough history and physical examination during the pandemic to identify the other causes of ARDS and avoid the negative effects of frequency bias.

A case of granulomatosis with polyangiitis complicated by COVID-19: Challenges in diagnosis and management

Case report-IntroductionGranulomatosis with Polyangiitis (GPA) is a rare small-to medium-vessel vasculitis associated with anti-neutrophil cytoplasmic autoantibody (ANCA). Its multi-systemic features include pulmonary, ear, nose, and throat (ENT), renal, and neurological manifestations. Its incidence is estimated to be 10.2 cases per million population. It is challenging to diagnose when its symptoms are treated in isolation from one another. This case highlights the difficulty in diagnosing GPA in a patient with respiratory symptoms during the Coronavirus Disease 2019 (COVID-19) pandemic and describes the challenges of managing it in the context of a subsequent COVID-19 infection as the mainstay of treatment remains immunosuppression.Case report-Case descriptionA 78-year-old female non-smoker with a history of leg ulcers developed a 3-month history of cough and haemoptysis and was treated in primary care for suspected sinus and chest infections. She then presented to Accident and Emergency twice for the same symptoms and was discharged after having her antibiotics changed.2 weeks later, she presented for the third time with cough, ongoing haemoptysis, conjunctivitis in the right eye, pain over the right side of her head, and discharge from her right ear. She was admitted as she was pyrexical, tachycardic and her CRP was 60. COVID-19 swabs were negative. ENT team recommended IV ceftriaxone and metronidazole for suspected orbital cellulitis. Blood cultures remained negative. CT sinuses with contrast showed right sided thrombosis of transverse sinus and bilateral mastoid effusion of the middle ear. Following neurology review, she was anticoagulated with dalteparin. A day later, she was transferred to the Respiratory ward and dropped her Haemoglobin level to 70. Her chest radiograph showed diffuse alveolar haemorrhage and CT images showed widespread bilateral peri-hilar consolidation.A rheumatology opinion was sought and vasculitic screen showed ANCA 268, and PR3 >177. Her urinary protein/creatinine ratio was elevated at 90. Rheumatology team confirmed multi-systemic GPA and recommended starting oral Prednisolone 60 mg daily. After the renal team was consulted, she was moved to a side-room and started on IV Methylprednisolone (pulsed with three doses), along with cyclophosphamide and rituximab. Dalteparin was discontinued.2 days later, she desaturated, and became pyrexical. Repeat COVID-19 swabs were positive.Three Consultants agreed that Plasma Exchange and Non-Invasive Ventilation (NIV) would be inappropriate. A Do Not Attempt Resuscitation form was signed, and prognosis was discussed with the patient and her 78-year-old husband who requested to visit. Patient deteriorated and unfortunately died 6 days later.Case report-DiscussionThis case is interesting because it highlights the diagnostic challenge of GPA. Retrospectively, it may be noted that doctors persisted in treating suspected infection although the patient continued to deteriorate. However, a diagnosis should be re-considered if the patient does not respond to treatment and it is important to consider vasculitis as a cause of haemoptysis.Anticoagulation was started since the benefits were considered to outweigh the risks as her haemoptysis was of small volume. The patient soon developed pulmonary haemorrhage, so the risks of anticoagulation should not be underestimated in vasculitis.The Rheumatology team's cautious approach to immunosuppression was in stark contrast to the renal team's aggressive approach. The Renal team believed that concerns about protecting the patient from COVID-19 when she was negative from this infection should not take precedence over appropriate immunosuppression from a potentially fatal vasculitis.The patient was admitted at the start of the COVID-19 pandemic and was negative for COVID-19 on admission. She was nursed in a bay on the Respiratory ward where she later became COVID-19 positive. This raises questions about whether the earlier test was a false negative result or whether her infection was hospital-acquired. Infection cont ol guidelines were changing rapidly at the start of the COVID-19 pandemic.The decision to avoid plasma exchange was based on the findings of the PEXIVAS trial. NIV was avoided as it required a full-face mask to minimize particle dispersion but would pose an asphyxiation risk as patient was coughing up blood.Finally, the team learnt to be flexible in these extraordinary circumstances when dealing with the end-of-life decisions of the COVID-19 positive patient. Although her husband was a vulnerable person because of his age, he was given the opportunity to visit while wearing Personal Protective Equipment and agreed to self-isolate for two weeks.Case report-Key learning pointsThis case helped me appreciate the complexity of deciding to immunosuppress an already severely ill patient in the context of the COVID-19 pandemic. I recognised that the patient had a poor prognosis with or without immunosuppression and our role as healthcare professionals was to give her the best chance of recovery. The conference will allow me to interact with other colleagues and discuss what they would do in this situation as our Rheumatology and Renal teams had different approaches.After further reading on false negative results, we found that Johns Hopkins researchers found that testing people for SARS-CoV2 too early in the course of infection is likely to result in a false negative test even though they may eventually test positive for the virus.I have also learnt about the PEXIVAS trial which found that the addition of plasma exchange to standard therapy does not reduce the risk for all-cause mortality among patients with severe ANCA-associated vasculitis. Moreover, a reduced-dose regimen of glucocorticoids is non-inferior to a standard-dose protocol, while reducing the risk for serious infections.Diffuse alveolar haemorrhage (DAH) is not treatable with arterial embolization or bronchoscopic methods due to the diffuse nature of the bleeding. Extracorporeal membrane oxygenation (ECMO) has been used to support patients with DAH but the use of ECMO is controversial due to the need for anticoagulation.The conference will help me deepen my understanding of epidemic rheumatology which will be useful for my clinical practice going forward, especially if there is a second wave of the COVID-19 pandemic. I am keen to use this event to engage with other clinicians on immunosuppression in the context of infection so that I may confidently manage similarly complex cases in the future.