Chilblain lupus erythematosus associated with systemic lupus erythematosus: A classic diagnosis in a current epidemiological context

Objectives: Chilblain lupus erythematosus (LE) is a rare chronic cutaneous lupus erythematosus (CCLE) characterized by the appearance of violaceous plaques in acral regions most exposed to cold. The isolated form affects middle-aged women, while the familial form manifests in early childhood and is associated with mutations in the TREX1 gene. Result(s): A 13-year-old adolescent, with no relevant family history, was referred in March 2021 for suspected chilblain-like lesions associated with COVID-19 infection. The patient presented with multiple violaceous papules on hands and feet. The lesions were slightly painful. Small hyperkeratotic papules were also observed on finger pads. Physical examination also revealed some aphthae affecting the lips. No other systemic symptoms were reported. A skin biopsy and blood tests were performed due to presumed chilblain LE with probable systemic involvement. Histology revealed basal vacuolar damage and intense perivascular and periadnexal lymphocytic inflammatory dermal infiltrate. Remarkably, mucin was noted among the collagen bundles. Leukopenia and positive ANA antibodies (titre 1:320) were detected. Complement levels were normal. SARS-CoV2 infection was ruled out. Skin lesions disappeared within 1 month under topical corticosteroids. Hydroxychloroquine was afterwards started by Rheumatology without recurrence of skin symptoms until last follow-up. Discussion(s): We present an uncommon case of an adolescent with systemic LE presenting as chilblain LE. Chilblain LE can be accompanied by other discoid CCLE. It can progress to systemic LE in up to 20% of patients, especially when concomitant CCLE is present. This rare presentation of CCLE should be differentiated from typical chilblain and other resembling lesions, such as SARS-CoV2-associated chilblain and acral purpuric lesions (COVID toes). The Mayo Clinic diagnostic criteria can be helpful, particularly in this last SARS-CoV2 outbreak scenario, when the reporting of similar skin lesions has been significant.

An occurrence of immune-mediated necrotizing myopathy following treatment of polymyositis in a Filipino female: A case report

Background: Necrotizing myopathy has been previously described but was not included in the Peter and Bohan criteria until 2004, when immune-mediated necrotizing myopathy (IMNM) was distinguished from polymyositis (PM) based on immunologic and histopathologic differences. IMNM is currently a well-recognized autoimmune myopathy and represents up to 20% of these cases. Case: A 60-year- old female with biopsy-proven PM achieved sustained clinical remission with Rituximab. Her co-morbid conditions include hypertension, diabetes mellitus, and dyslipidemia. The patient noted a recurrence of gradual progressive, proximal muscle weakness and easy fatigability after receiving her first mRNA Covid-19 vaccine. Four months after onset of symptoms, CK Total was 9600 U/L. Rituximab was administered and muscle weakness and total CK levels (1247 U/L) improved within 10 days. She was prescribed rosuvastatin and fenofibrate for dyslipidemia within 7 days of completing the rituximab course. Two weeks later, proximal muscle weakness recurred. She became wheelchair-bound and experienced dysphonia. MMT score was 2/5 in proximal muscles and total CK total increased to 19,935 U/L. The patient received Methylprednisolone 500 mg IV once a day for 3 days. She had a good response with resolution of dysphonia and improvement of MMT to 4/5 on shoulder abduction and hip flexion on the 6th hospital day. She was discharged on oral methylprednisolone at 1 mg/kg/day. Muscle biopsy was consistent with an immune-mediated necrotizing myopathy, revealing necrotic fibers, intracellular macrophages, fatty infiltrates, irregular staining patterns on NADH stain with no evidence of endomysial inflammation, perifascicular atrophy, ragged red fibers, or rimmed vacuoles. Antibodiy against 3-hydoxy- 3- methylglutarylcoenzymeA reductase (HMGCR) result is pending but the other myositis-specific antibodies are negative.(including anti-SRP). Conclusion(s): IMNM is an autoimmune myopathy associated with anti-HMGCR and anti-SRP antibodies that clinically present similarly to polymyositis. The temporal occurrence of worsening muscle weakness with initiation of statin therapy make statin toxic myopathy or immune mediated necrotizing myopathy as diagnostic considerations. This case emphasizes the need to re-evaluate the etiology of new onset muscle weakness in patients with idiopathic inflammatory myopathy and highlights the role of myositis-specific antibodies and muscle biopsy in confirming the diagnosis.

Circulating histones as common mediators in classical and COVID-19 Sepsis: novel triggers for monocyte and MDW alterations

Background: Histones (i.e., positively charged nuclear proteins) are key components in chromatin functions that under physiological conditions contribute to DNA packaging and regulate gene expression, but they are significantly mobilized in blood and body fluids during cell and tissue injuries in several pathological processes. Histones mediate both inflammatory pathways and coagulative cascade, crucially linked to the severity and mortality of many human pathologies (e.g., thrombosis, sepsis, COVID-19). SARS-CoV-2 and sepsis infections share common laboratory biomarkers, such as Monocyte Distribution Width (MDW), that is mainly linked to the heterogeneity of monocyte volume;these modifications, upon massive inflammatory activation, predict multiorgan dysfunction and increased mortality rate in several pathological conditions. No data are available on the roles of histones as MDW modifiers. Method(s): Comparison of MDW index was undertaken by hematology analyzer UniCell DxH900 Hematology Analyzer (Beckman Coulter) on whole blood samples from patients with COVID-19 and Sepsis. The impact of histones on the MDW characteristics was assessed by the in vitro time-dependent treatment of healthy control whole blood with histones and histones+lipopolysaccharide. Result(s): We demonstrated the breadth of early, persistent, and significant increase of MDW index in whole blood from healthy subject treated in vitro with histones, highlighting changes similar to those found in vivo in classic and viral sepsis patients. The findings of MDW changes are confirmed by digital microscopy of blood smears, highlighting the histone-induced modifications of cell volume, cytoplasmic vacuolization, and nuclear structure alterations of the circulating monocytes. Conclusion(s): Histones contribute to the pronounced and persistent monocyte alterations observed in classical and viral sepsis. Assessment of the biological impact of circulating histone released during COVID-19 and sepsis on monocytes should be considered as key factor modulating both thrombosis and inflammatory processes, as well as the importance of neutralization of their cytotoxic and procoagulant activities by several commercially available drugs (e.g., heparins and heparinoids).

Role of copper levels in patients with myelodysplastic syndromes

Background: Patients with inadequate amounts of copper often present with cytopenias and exhibit dysplasia on bone marrow, mimicking myelodysplastic syndrome (MDS) and pose diagnostic difficulties. Method(s): This cross-sectional observational study was performed from January 2020 to June 2021. Patients diagnosed with MDS were included in the study and serum copper levels were measured by the Inductively Coupled Plasma Mass Spectrometry (ICPMS) method. Copper supplementation with intravenous copper chloride 2.5mg daily for the first two weeks, followed by oral 3mg copper sulfate thrice daily for the next three months, was given for copper-deficient patients. Response assessment was performed with repeat hemogram and serum copper levels. Result(s): A total of 57 patients were diagnosed with MDS, of these, 33 (57.89%) were males and 24 (42.10%) were females. The mean age was 54.3+/-14.6 years (13-81). The distribution of patients in different types of MDS was MDS-SLD in 15, MDS-MLD in 18, MDS-EB1 in 7, MDS-EB2 in 8, and MDS-U in 9 patients. Anemia was seen in (87.71%) of patients, with mean hemoglobin 7.6+/-2.1g/dL (4.6-14.5g/dL). Neutropenia was seen in 31 (54.38%) with a mean absolute neutrophil count(ANC) of 2073+/-2139/muL (211-10,952/muL). Thirty seven (64.91%) patients had thrombocytopenia with a mean platelet count of 1,05,298+/-1,21,769/muL (9,000-6,74,000/muL). The mean serum copper levels were 146.69+/-42.36mug/dL (54.2-254.0mug/dL). Only three (5.26%) patients out of 57 were found to have copper deficiency. All three patients with low copper levels were found to have anemia, thrombocytopenia, and mildly raised serum erythropoietin levels. All three patients had dyserythropoiesis on bone marrow examination, and only one patient each had cytoplasmic vacuolations in erythroid precursors and dysmegakaryopoiesis. Among the three patients with copper deficiency, two patients had significant improvement in cytopenias after copper supplementation, and one had lost follow-up due to COVID-19. Conclusion(s): This study is the first from India to evaluate the role of copper in patients presenting with predominantly hematological manifestations. For patients presenting with cytopenias or marrow dysplasia resembling MDS, copper deficiency should be considered in the differential diagnosis. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest. Copyright © 2022

Glomerular Annexin A3 and Cathepsin C Staining in COVID-19-Associated and HIV-Associated Nephropathy (HIVAN)-Associated Collapsing Glomerulopathy

Background: Prior studies demonstrated glomerular tuft staining for annexin A3 (Anxa3), a marker of parietal epithelial cells (PECs), and cathepsin C (Ctsc), a master regulatory protease, distinguishing primary collapsing glomerulopathy (CG) from other glomerular diseases. We hypothesized these staining patterns would differentiate COVID-19 associated CG (COVID-19+/CG+) from COVID-19(+) without CG (COVID-19+/CG-). Method(s): Biopsy sections used were from patients with COVID-19 infections and a pathologist-based tissue diagnoses including CG (COVID-19+/CG+;n=4) or lacking CG diagnosis (COVID-19+/CG-;n=6) were stained for Anxa3 and Ctsc using published protocols. HIVAN-associated CG (n=4) biopsies were used as a secondary CG control. Historical controls data for non-CG biospies (PMID:32561683). Glomerular staining was tabulated as for PEC staining, phenotypic characteristics of normal and activated (enlarged nuclei, hypertrophic/enlarged cuboidal shape cells, vacuolization) PECs, and for glomerular tuft to Bowman's capsule adhesions or cellular PEC bridges. Globally scarred glomerulii were omitted from analysis. Serial section staining was used to demonstrate Anxa3 and Ctsc co-localization. Differences in the mean (i) number of glomeruli staining OR (ii) glomerular tuft area stained for Anxa3 and Ctsc per biopsy were compared by one-tailed t-test assuming an increase in staining in CG over non-glomerular disease. A p-value <0.05 was used for statistical significance. Result(s): All COVID-19+/CG+ and HIVAN patients with CG demonstrated extensive Anxa3 and Ctsc glomerular tuft staining. The frequency of glomerular tuft Anxa3 and Ctsc staining and percent glomerular area was significantly (p<0.05) increased in biopsies with COVID-19+/CG+, compared to COVID-19+/CG- (log2FC 2.8-2.9). No statistical difference in frequency or area stained for Anxa3 and Ctsc was observed between COVID-19+/CG+ and HIVAN-associated CG. Conclusion(s): Anxa3 and Ctsc glomerular tuft expression is increased significantly in COVID-19 and HIVAN patients with CG, mirroring our findings in primary CG. These data support the hypotheses that (a) migration of activated PECs into the glomerular tuft is a prevalent event in both primary CG and virus-associated secondary CG, and (b) glomerular Anxa3 or Ctsc may be theragnostic biomarkers of CG.

Probenecid-Induced IgA Nephropathy Is Reversible

Introduction: IgA nephropathy is usually idiopathic in nature but can have a genetic predisposition & it can also be secondary to autoimmune diseases, vasculitis, infections, liver disease, or anti-VEGFdrugs like bevacizumab, & covid vaccine. We present a case of probenecid-induced IgA nephropathy. Case Description: A 65-year-old male with chronic gout developed progressive chronic kidney disease over a 3-year period. He had been on probenecid 1 g twice daily for his gout for 15 yrs. His sodium iothalamate clearance deteriorated to 58 mL/min, with a serum creatinine of 1.5 mg/dL. All other serologic tests were negative. His 72-hour lead level was also normal. He did not have SLE, granulomatous disease, or systemic rheumatic disorders. Suprisingly he did not have proteinuria or hematuria. Renal biopsy revealed IgA nephropathy, with segmental mesangial hypercellularity, mild arterial sclerosis, & tubular atrophy. Cytoplasmic lipofuscin pigment was noted on PAS stain capillary loops with focal thickening of the glomerular basement membrane, engorged capillary loops, & thickened tubular basement membrane. Immunofluorescence studies showed diffuse segmental paramesangial granules of IgA [3+] & fibrinogen as well as paramesangial granules of IgG [2+], Kappa & lambda. Electron microscopy showed swollen podocytes with increased cytoplasmic organelles and vacuolization, focal foot process effacement, & electron-dense deposits in the paramesangium & mesangium. His MEST score was zero. 6 months after discontinuation of probenecid, the patient's iothalamate GFR significantly improved to 79 mL/min, followed by 82 mL/min 6 months later. He never had proteinuria, hematuria, or casts throughout his disease course. Five years later his GFR was 88 ml/min with a serum creatinine of 1.1 mg/dl. Discussion(s): Probenecid has pleiotropic effects on the human immune system. It inhibits Pannexin-1 channels which are known to modulate T-cell function. Probenecid also regulates TRPV -2 channels as an agonist. These channels are also present on human immune B and T cell lymphocytes. Probenecid inhibits VEGF in retinal endothelial cells, & bevacizumab, an anti-VEGF monoclonal antibody, has been shown to cause IgA nephropathy. We conclude that probenecid can be a cause of IgA nephropathy which is reversible upon drug discontinuation.

SEVERE ALLERGIC ERYTHEMATOUS REACTION POSTMESSENGER RNA-BASED COVID-19 VACCINE

SESSION TITLE: Issues After COVID-19 Vaccination Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Covid 19 pandemic has infected 125 million people so far (1). The development of safe and effective vaccines is crucial to lessen the impact of SARS-COV 2 on global health. Some adverse events of the covid 19 vaccination have been reported including few dermatological reactions. We report a case of severe allergic erythematous drug reaction that occurred 3 days after the second dose of messenger RNA (mRNA) Pfizer vaccine. CASE PRESENTATION: A 42 year old female with past medical history of Grover's disease and Multiple Sclerosis presented to the Emergency department from the nursing home with complaints of erythematous, scaly, painful rash that occurred 3 days after the second dose of mRNA covid 19 vaccine. Patient states she had a generalized rash after the first dose of vaccine but it resolved spontaneously and did not require treatment. This time the rash started on the scalp and gradually progressed to the rest of the body. It was associated with severe itching, burning and serosanguinous discharge. Patient did not report any change in medication, use of new detergent or contact with an offending agent. The patient denied fever, chills, nausea, vomiting, diarrhea, constipation, abdominal pain, chest pain or palpitations. She had no history of similar complaints in the past. On physical examination, she was afebrile and hemodynamically stable but in severe distress due to pain. The rash covered 95% of the body surface area and was more severe around the mouth, in the axilla, neck and the inframammary area. Erosions could be seen in the skin folds with serosanguinous discharge. The laboratory results were positive for eosinophilia with absolute eosinophil count of 0.7. Remaining laboratory results were within normal limits. The pathology report for the erythematous rash was consistent with drug reaction. A slight vacuolar degeneration along the dermal epidermal junction with few apoptotic keratinocytes were noted. A compact horn and band-like lymphoid infiltrate were also noted. The patient was started on high dose steroids, analgesics and antihistamines. Petroleum gel impregnated gauze was used for dressing. She was placed in the intensive care unit for careful monitoring. Her rash resolved gradually and her symptoms improved. DISCUSSION: mRNA vaccines are associated with type 1 interferon responses that result in inflammation and autoimmune conditions. This could explain the skin manifestations associated with these vaccines. Allergenic components in the vaccines could also be a possible cause of these reactions. A patch test can be performed to prevent these reactions in susceptible individuals. CONCLUSIONS: This report highlights the need for vigilance to detect severe allergic reactions after covid 19 vaccination to improve the safety of the vaccine. Reference #1: WHO coronavirus (COVID-19) dashboard. [ Jul;2021 ];https://covid19.who.int/ 2021 DISCLOSURES: No relevant relationships by Ruhma Ali No relevant relationships by Sneha Bijoy No relevant relationships by Chrystina Kiwan no disclosure on file for Richard Miller;No relevant relationships by Aditya Patel No relevant relationships by jihad slim, value=Honoraria Removed 03/25/2022 by jihad slim No relevant relationships by jihad slim, value=Honoraria Removed 03/25/2022 by jihad slim No relevant relationships by jihad slim, value=Honoraria Removed 03/25/2022 by jihad slim No relevant relationships by jihad slim, value=Honoraria Removed 03/25/2022 by jihad slim No relevant relationships by jihad slim, value=Honoraria Removed 03/25/2022 by jihad slim

E-CIGARETTE OR VAPING USE-ASSOCIATED LUNG INJURY (EVALI): EFFECTS OF VAPING OR COVID-19?

SESSION TITLE: Critical Care in Chest Infections Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: EVALI is an acute lung injury that occurs due to the use of e-cigarettes or vaporizer products that usually contain THC or nicotine. There was an outbreak of EVALI in 2019. This is a diagnosis of exclusion with foamy macrophages with pneumocyte vacuolization being the best diagnostic clues. (1) Vitamin E acetate laced products seem to be the causing factor. CASE PRESENTATION: A 34-year-old female presented to the emergency department due to increasing shortness of breath, fever, pleuritic chest pain, cough, and headaches for the last 9 days. Two days prior she presented to urgent care where she was given an albuterol inhaler and azithromycin. At arrival, the patient was found to have tachycardia with a rate of 120-130, afebrile, SpO2 at 96% on room air, BP at 100/59. Her initial workup was grossly normal except for an elevated WBC and elevated D-Dimer. Chest X-ray revealed opacities in the lower lungs consistent with pneumonia. CTA of the chest revealed patchy pulmonary opacities consistent with COVID pneumonia. She took three separate SARS-CoV-2 PCR tests which all came back negative. The patient underwent a large workup which included infectious disease, pulmonology, and cardiology consults. She was treated with broad-spectrum antibiotics for the presumed diagnosis of pneumonia but her condition quickly deteriorated, eventually requiring 6L of O2 via nasal cannula. Screening for a large array of bacteria, fungus, and viruses all resulted negative. Upon further discussion with the patient, she admitted to smoking a THC vaporizer every night for the last seven months and that she had recently purchased a new fluid for her THC vaporizer through the internet. Bronchoscopy was also acquired but did not show any specific findings, including being negative for eosinophils. Discontinuation of antibiotics and initiation of IV steroids treatment provided rapid improvement of the patient's condition. Based on her history of THC vaping, the clinical presentation of fever, hypoxia, her chest x-ray, and chest CT showing extensive lung infiltrates, infections were ruled out and the most likely diagnosis of EVALI was made which responded well to steroids. DISCUSSION: COVID and EVALI initially can present similarly as respiratory problems, fever, and the need for oxygen. It is important to gather history on the patient as a vaping history is needed to suspect EVALI as imaging can show a wide range from ground-glass opacities to acute hypersensitivity pneumonitis. (2) CONCLUSIONS: There are some distinguishing features of EVALI from COVID one being in EVALI there is a large increase in the white count and lastly the response to steroids is the key (2). Steroids are the primary care for someone with EVALI with most patients recovering in 1-3 days with the use of steroids. (2) Reference #1: Bierwirth, A., Orellana, G., Milazzo, E. and Hamdan, A., 2020. TETRAHYDROCANNABINOL VAPING-ASSOCIATED LUNG INJURY (EVALI): A US EPIDEMIC?. Chestnet Journal. Reference #2: MacMurdo, M., Lin, C., Saeedan, M., Doxtader, E., Mukhopadhyay, S., Arrossi, V., Reynolds, J., Ghosh, S. and Choi, H., 2020. e-Cigarette or Vaping Product Use-Associated Lung Injury. Chestnet Journal. DISCLOSURES: No relevant relationships by Narden Gorgy No relevant relationships by Matheus Moreira Sanches Peraci No relevant relationships by George Walbridge No relevant relationships by John Zakhary

HYDROXYCHLOROQUINE CAN BREAK YOUR HEART

SESSION TITLE: The Cardiac Intensivist 2 SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Hydroxychloroquine and chloroquine are medications derived from aminoquinoline. They are disease-modifying antirheumatic drugs used in the treatment of systemic lupus erythematosus (SLE). Although well tolerated, they do have side effects such as retinopathy, vacuolar myopathy, neuropathy, and as seen in our patient, cardiotoxicity. CASE PRESENTATION: Patient is a 48 year old female with a past medical history significant for chronic kidney disease secondary to autosomal dominant polycystic kidney disease, SLE on hydroxychloroquine who presented to the emergency department complaining of weakness. On arrival the patient was found to be in cardiogenic shock. Her transthoracic echocardiogram revealed a reduced ejection fraction of 37% and a large pericardial effusion concerning for tamponade physiology. Her COVID-19 PCR test was positive. She was taken for emergent pericardiocentesis which revealed 300cc of exudative fluid. Patient’s right heart catheterization revealed mean pulmonary capillary wedge pressure of 23 mmHg, pulmonary artery pressures of 44 mmHg/24 mmHg, mean 31mmHg, cardiac index 1.1L/min/m² by thermodilution, 1.7 L/min/m² by Fick. Following right heart catheterization and intra aortic balloon pump placement, the patient was admitted to the medical intensive care unit (MICU) and placed on intravenous inotropic and vasopressor support. Shortly after arrival to the MICU, patient had an increase in vasopressor requirements. Bedside ultrasound revealed cardiac tamponade. Patient had approximately 400cc of bloody pericardial fluid removed from her pericardial drain. The decision was made for emergent venoarterial extracorporeal membrane oxygenation (ECMO) to be initiated. Endomyocardial biopsy was performed which revealed vacuolization in the cytoplasm of several myocytes as well as lymphocytes in the interstitium of the endocardium. The vacuoles found in the cardiac myocytes were PAS positive. These biopsy results are consistent with hydroxychloroquine cardiotoxicity. The patient’s hydroxychloroquine was discontinued. In addition to hemodynamic support, she also received intravenous immunoglobuluin and systemic steroids. After a prolonged hospitalization she was successfully discharged. DISCUSSION: Cardiotoxicity is a rare adverse reaction seen with hydroxychloroquine. A 2018 systematic review revealed 127 cases of cardiac toxicity associated with the use of hydroxychloroquine or chloroquine. Most patients had been treated with the medication for a prolonged period of time and the toxicity is dose dependent. The mechanism behind hydroxychloroquine and chloroquine induced cardiomyopathy is believed to be secondary to lysosomal dysfunction as a result of toxic phospholipid accumulation in cardiomyocytes. CONCLUSIONS: In patients with new onset cardiomyopathy, a detailed medication reconciliation should be conducted to evaluate for toxins such as hydroxychloroquine and chloroquine. Reference #1: Della Porta, A., Bornstein, K., Coye, A., Montrief, T., Long, B., & Parris, M. A. (2020). Acute chloroquine and hydroxychloroquine toxicity: A review for emergency clinicians. The American Journal of Emergency Medicine. Reference #2: Abbi, B., Patel, S., Kumthekar, A., Schwartz, D., & Blanco, I. (2020). A Case of Cardiomyopathy With Long-term Hydroxychloroquine Use. JCR: Journal of Clinical Rheumatology, 26(8), e300. Reference #3: Chatre, C., Roubille, F., Vernhet, H., Jorgensen, C., & Pers, Y. M. (2018). Cardiac complications attributed to chloroquine and hydroxychloroquine: a systematic review of the literature. Drug safety, 41(10), 919-931. DISCLOSURES: no disclosure on file for Joseph Adams;no disclosure on file for Suliman Alradawi;No relevant relationships by George Kalapurakal No relevant relationships by Mohammed Siddiqui

LUNG INVOLVEMENT in VEXAS SYNDROME

Background: Vacuoles, E1 enzyme, X-linked, autoinfammatory, somatic (VEXAS) syndrome is a recently identifed disorder caused by somatic mutations in the UBA1 gene of myeloid cells. Various manifestations of pulmonary involvement have been reported, but a detailed description of lung involvement and radiologic fndings is lacking. Objectives: To describe lung involvement in VEXAS syndrome. Methods: A retrospective cohort study was conducted of all patients iden-tifed at the Mayo Clinic with VEXAS syndrome since October 2020. Clinical records and chest high resolution computed tomography (HRCT) scans were reviewed. Results: Our cohort comprised 22 white men with a median age of 69 years (IQR 62-74, range 57-84). Hematologic disorders including multiple myeloma, myelodysplastic syndrome and pancytopenia were present in 10 patients (45%), rheumatologic diseases including granulomatosis with poly-angiitis, IgG4-related disease, polyarteritis nodosa, relapsing polychondritis, and rheumatoid arthritis were found in 10 patients (45%), and 4 patients had dermatologic presentations including Sweet syndrome, Schnitzer-like syndrome or drug rash with eosinophilia skin syndrome (DRESS). VEXAS syndrome-related features included fever (18, 82%), skin lesions (20, 91%), lung infiltrates (12, 55%), chondritis (10, 45%), venous thromboembolism (12, 55%), macrocytic anemia (21, 96%), and bone marrow vacuoles (21, 96%). Other manifestations observed were arthritis, scleritis, hoarseness and hearing loss. Median erythrocyte sedimentation rate (ESR) was 69 mm/1st hour (IQR 34.3-118.8) and median C-reactive protein (CRP) of 55.5 mg/dL (IQR 11.4-98.8). The somatic mutations affecting methionine-41 (p.Met41) in UBA1 gene were: 11 (50%) p.Met41Thr, 7 (32%) p.Met41Val, 2 (9%) p.Met41Leu, and 2 (9%) in the splice site. All patients received glu-cocorticoids (GC) (median duration of treatment was 2.6 years);21 (96%) received conventional immunosuppressive agents (methotrexate, aza-thioprine, mycophenolate, leflunomide, cyclosporin, hydroxychloroquine, tofacitinib, ruxolitinib) and 9 (41%) received biologic agents (rituximab, tocilizumab, infliximab, etanercept, adalimumab, golimumab, abatacept). Respiratory symptoms included dyspnea and cough present in 21 (95%) and 12 (55%), respectively, and were documented prior to VEXAS diagnosis. Most of the patients were non-smokers (14, 64%) and obstructive sleep apnea (OSA) was present in 11 patients (50%). Seven patients (32%) used non-invasive ventilation, 6 used C-PAP, and 1 used Bi-PAP. Bronchoalveolar lavage (BAL) was available in 4 patients, and the findings were compatible with neutrophilic alveolitis in 3. Two patients had lung biopsies (2 transbronchial and 1 surgical) that showed ATTR amyloidosis and organizing pneumonia with lymphoid interstitial pneumonia, respectively. Pulmonary function tests were available in 9 (41%) patients and showed normal results in 5;3 patients had isolated reduction in DLCO and 1 with mild restriction. On chest HRCT, 16 patients (73%) had parenchymal changes including ground-glass opacities in 9, septal thickening in 4, and nodules in 3;pleural effusions were present in 3 patients, air-trapping in 3 patients and tracheomalacia in 1 patient. Follow-up chest HRCT was available for 8 patients (36%), the ground-glass opacities resolved in 5 patients, 3 patients manifested new or increased ground-glass opacities, and 1 patient had increased interlobular septal thickening. After 1 year of follow-up, 4 patients (17%) had died;3 due to pneumonia (2 COVID-19,1 bacterial) and 1 due to heart failure. VEXAS flares occurred in 18 patients (82%), the maximum number of relapses was 7, and they were mainly managed with GC and with changes in the immuno-suppressive regimen. Conclusion: Pulmonary involvement was documented by chest HRCT in most patients with VEXAS syndrome. Respiratory symptoms occurred in over one half of patients and about 20% had PFT abnormalities. The pulmonary manifestations of VEXAS are nonspecifc and characterized predominantly by infamma-tory parenchymal involvement.

Erythema multiforme related to AstraZeneca SARS-CoV-2 vaccine

A 44-year-old man of Pakistani origin presented to emergency 6 days following his first dose of the AstraZeneca (AZ) SARSCoV- 2 vaccine. He developed flu-like symptoms followed by erythematous pruritic rash. Physical examination showed a maculopapular rash associated with purpura and targetoid lesions affecting his distal extremities, trunk and mucous membranes. He also had crusting and ulceration of his oral and genital mucosal areas. He had no other significant past medical history. A biopsy was taken from his right arm and sent for urgent histology and direct immunofluorescence. Histology revealed parakeratotic scale with interface dermatitis comprising basal layer vacuolation and lymphocyte exocytosis. The epidermis showed prominent dyskeratotic keratinocytes scattered throughout the epidermis. The papillary dermis showed a mild perivascular lymphocytic infiltrate including eosinophils and melanophages. Other investigations showed leucocytosis (12 × 109 L-1), high eosinophils (0.9 × 109 L-1), raised liver enzymes with alkaline phosphatase 159 U L-1 and alanine aminotransferase 172 U L-1. A full infection screen, including herpes simplex virus, SARS-CoV-2 and atypical viral infection, was negative. Immunology was also reported as negative. Based on the findings, a diagnosis of erythema multiforme (EM) secondary to AZ vaccine was made. He was treated with topical steroids and emollients, leading to resolution of his skin and mucosal areas in 4-6 weeks. Recently, there have been a few reported cases of EM in patients with COVID-19 (Jimenez-Cauhe J, Ortega-Quijano D, Carretero- Barrio I et al. Erythema multiforme-like eruption in patients with COVID-19 infection: clinical and histological findings. Clin Exp Dermatol 2020;45: 892-5) and two patients who have had the Pfizer-BioNTech vaccine [Kim M, Kim J, Kim M et al. Generalized erythema multiforme-like skin rash following the first dose of COVID-19 vaccine (Pfizer-BioNTech). J Eur Acad Dermatol Venereol 2021], but the information is limited. Our case emphasizes the need for further studies into the cutaneous adverse effects related to COVID-19vaccines.

PATHOLOGICAL CHANGES IN THE KIDNEYS IN PATIENTS WITH ACUTE RENAL INJURY DUE TO CORONAVIRUS INFECTION

INTRODUCTION AND OBJECTIVE: Acute kidney injury (AKI) in coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus is much more common than previously thought and is associated with severe disease and high mortality. Despite the fact that the respiratory and immune systems are the main targets of the COVID- 19 virus, AKI is also observed, identified by the occurrence of proteinuria or hematuria, an increase in serum urea and creatinine levels. The aim of the study is to assess the pathomorphological changes in the kidneys in 100 cases of autopsy of patients with COVID-19 using light microscopy and immunohistochemical diagnostic methods in order to clarify the possible mechanism of AKI. METHODS: The study was carried out using samples obtained from 100 patients, the time interval of the onset of the disease corresponded to the 4th wave of the peak of the incidence in Russia (from June 2021). The age of patients varied from 37 to 94 years 72 (s =12.5), men - 34, women - 66. Patients with chronic kidney disease, diabetes mellitus and cancer were not included in the analysis. The cause of death in all cases was acute respiratory failure, histologically defined as diffuse alveolar injury. AKI in accordance with the KDIGO criteria was detected in 34 patients. RESULTS: On light microscopy, diffuse massive damage to the proximal tubules with loss of the brush border, degeneration of vacuoles was detected in 46 patients, massive necrosis of the tubules in 11 patients. In 65 patients, an extremely pronounced congestion of paretic dilated vessels with widespread paravasal hemorrhages was revealed. Paravasal lymphoid infiltration of the vascular endothelium was detected in 27 patients. Severe sludge syndrome in small and medium-sized vessels in 46 patients. In almost all cases, hemosiderin granules and hyaline casts were found. The quantitative and qualitative composition of tissue macrophages corresponded to the population data, without visible correlations with the disease. CONCLUSIONS: According to the study, the factors contributing to AKI include systemic hypoxia, abnormal coagulation, increased catabolism due to fever, drug-related rhabdomyolysis or hyperventilation with increased serum degradation products. Thus, our research provides evidence for AKI during the progression of COVID-10. These results contribute to a better understanding of the course and progression of SARS-CoV-2 virus infection.

Morphologic Features of Peripheral Blood Smears in COVID-19 Infection

Background: At the end of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a novel coronavirus responsible for causing the global coronavirus disease 19 (COVID-19) pandemic. Symptoms range from asymptomatic to severe respiratory symptoms. SARS-CoV-2 infection is well known to be associated with immune dysregulation and hematologic aberrancies. Few studies have reviewed peripheral blood smears abnormalities from COVID-19 patients. In this study, we aimed to characterize the morphologic features of peripheral blood smears from COVID-19 patients. Design: Hospitalized patients with PCR-confirmed COVID-19 infection were identified. Complete Blood Count (CBC) data, clinical findings, and peripheral blood morphology were compared to control patients with confirmed negative COVID-19 PCR. Results: Twelve PCR confirmed covid 19 positive patients (male- 9, female- 3) with an age range 38 to 95 were compared to 11 control patients PCR-negative for COVID-19. Most patients presented with fever or respiratory symptoms. Among the COVID-19 positive patients absolute lymphopenia was seen in 9/12 patients. Absolute monocytosis was seen in 2/12 and monocytopenia was seen in 3/12 cases. Interestingly, large, activated monocytes with abundant gray-blue cytoplasm with prominent cytoplasmic vacuoles were seen in all the COVID-19 positive patents (see fig. 1 D-F) as compared to normal controls. These activated monocytes consist of 1-11% of leukocytes, with absolute counts ranging from 0.12-0.69 x 10∧3/microliter. Other morphologic findings found in peripheral blood smears include plasmacytoid and atypical lymphocytes (Fig 1A-C), as well as neutrophils with pseudo-Pelger-Huet nuclei (Fig 1G-I). 10/12 patients with COVID-19 infection were unvaccinated;differences between peripheral blood smears from vaccinated and unvaccinated patients were not seen. All patients recovered upon follow up. Conclusions: In conclusion, activated monocytes with distinct morphology are present in varying numbers in the peripheral blood from hospitalized COVID-19 patients. These activated monocytes are not present in non-COVID-19 patients. These findings are consistent with those found in previous studies. Some of these studies have shown the presence of activated monocytes may indicate favorable outcomes. (Figure Presented).

Morphology and Immunophenotype Correlation Study of Peripheral Blood from COVID19 Patients

Background: Since the first case of COVID19 infection in 2019, this RNA virus has led an unprecedented pandemic that infected more than 232 million people. Although the disease is studied extensively, much remains poorly understood. Here, we performed the first correlation study on the peripheral blood morphology and immunophenotype of the white blood cells (WBCs) from COVID19 patients. Design: A total of 52 samples from COVID19 patients and 15 blood samples as control group were analyzed. COVID19 patients were divided into two groups based on clinical severity, severe (respiratory failure) or non-severe (hospitalized but stable). The controls were the patients with negative COVID19 results by PCR and antibody tests. The WBC morphology was examined either by blood smear review or via CellaVision DM analyzer captured images. Navios flow cytometer and Beckman Kaluza C software were used for immunophenotype analysis. Two-tailed T-test was performed on the COVID19 groups and the control group Results: Almost all COVID19 patients showed marked neutrophilia and lymphopenia on the CBC tests. Morphologically, the neutrophils showed irregularities like hypogranulation, toxic granules and pseudo Pelger-Huet anomaly (Fig 1A). In severe COIVD19 group, there was an increase in neutrophils with immatures phenotypes, showing CD33 positivity while CD10, CD13 and CD16 negative (Fig 1B). Conversely, the CD10(+) mature neutrophils aberrantly expressed CD56 (Fig 1B). The percentage of CD56(+) neutrophils was significantly higher in both COVID19 groups, suggesting a stronger cellular adhesion and interaction. The monocytes from the COVID19 patients had increased cytoplasm with cytoplasmic protrusion and vacuolization (Fig 2A). Phenotypically they were positive for CD13, CD33, CD38 and HLA-DR. The lymphocytes were also atypical, including increased cytoplasm with large granules and vacuoles. Phenotypically, they are activated, expressing CD38, HLA-DR, and mainly α/β subtype. Giant platelets with cytoplasmic vacuoles and projections were easily seen. Platelet aggregations were observed (Fig 2B). These platelets were CD45(-) and expressed CD61 at lower-than-normal intensity, while expressing increased CD42b intensity when compared to the control group on a log scale. Conclusions: Despite being a small study, we were able to correlate the morphologic and phenotypic alterations of the WBCs in COVID19 patients. As such, this helped to explain some of the clinical hematologic manifestation of the disease. (Figure Presented).

Pancreatic histological studies in mice induced by alloxan and steeping okra coffee (Abelmoschus esculentus [L.] Moench)

Introduction: Those suffering from diabetes mellitus (DM) form one of the high-risk groups for developing severe illness from COVID-19. Steeping okra coffee (Abelmoschus esculentus [L.] Moench) is empirically used in DM treatment. Objective: To determine the pancreatic histology in mice induced by alloxan and steeping okra coffee (SOC). Method: This was an experimental research using 16 mice that were divided into four groups, 1) control group (alloxan and aquades) and SOC Group;2-4), treated with steeping okra coffee at 1820, 3640, and 5460 mg/KgBW concentration for ten days. Results: The treatment groups 2 and 3 showed an improvement in the damage of acinar cells and islets of Langerhans by 100%. On the other hand, there was still 25% vacuolisation on the islets of Langerhans in the group 4 treatment group. Conclusion: The steeping okra coffee repaired the islets of Langerhans cells and acinar cells that were vacuolised.

Pathological and Microbiological Findings in Free-Ranging Bats in Italy

Introduction: Recent studies have shown that bats are the reservoir hosts of several novel viruses, increasing the interest in bats as potential vectors of zoonotic pathogens. Several studies investigated the presence of infectious agents in bats, but their impact on the individual host and their importance on bat mortality is largely unknown. The aim of this study was to describe the microbiological and histopathological findings in 77 deceased bats belonging to nine European species (families Vespertilionidae and Molossidae). Materials and Methods: Bat carcasses were collected in the Piedmont region (Italy) by the Unconventional Rehabilitation Centre (CANC), Torino University, and submitted to necropsy. Species, age and sex of each bat were recorded. Virological (orthoreovirus, coronavirus, flavivirus, rhabdovirus, poxvirus, kobuvirus) and histopathological examinations were performed on the main organs (liver, spleen, kidney, gut, lung, heart and brain). Results: Traumatic injuries (fractures, haemorrhages, skin lesions;43%) and predation injuries (8.4%) represented the two main causes of death. Regardless of species, age and sex, the pathological examination revealed inflammatory/degenerative lesions mainly involving liver (non-suppurative hepatitis and vacuolar degeneration;20.8%) and lung (bronchopneumonia;29.9%). Coronavirus, flavivirus, rhabdovirus and kobuvirus were not detected. Poxviruses were detected in three lungs, two with pneumonia, and 14.3% of animals were positive for reoviruses. Conclusions: This study demonstrates the importance of inflammatory lesions in bat mortality, and shows that bats can harbour infectious agents. However, there is no evidence that Italian bats may represent a severe risk for human health.

White Blood Cells in COVID-19: A Study on Viral Induced Cytopathic Changes in the Peripheral Smear

Introduction: Laboratory parameters are crucial in diagnosis and prognosis of Coronavirus Disease 2019 (COVID-19). It would be of interest to explore morphological changes in infected White Blood Cells (WBCs). A detailed examination of peripheral smears may shed light on pathophysiology of infected cell lines and differentiate them from those in established viral infections like dengue and infectious mononucleosis. Aim: To study morphological changes of WBCs in peripheral smears of severe and non severe cases of COVID-19 patients. Materials and Methods: This cross-sectional study was conducted at a tertiary care centre, Dr. Chandramma Dayananda Sagar Institute of Medical Education and Research, Ramanagara, Karnataka, India, from April 2021 to August 2021 on 120 peripheral smears of adult COVID-19 positive cases. Abnormal morphological features were graded by counting 100 cells in each of neutrophils, lymphocytes and monocyte lineage. Changes were compared and analysed between severe and non severe groups using Statistical Package for Social Sciences (SPSS) software version 26.0. A p-value <0.05 was considered as significant. Results: The study included total of 120 cases (59 severe and 61 non severe) with a mean age of 47 years. Male to female ratio in severe and non severe categories were 1:1.2 and 1:0.6, respectively. Severe category patients (n=59) were associated with statistically significant leucocytosis (p-value=0.04), absolute neutrophilia (p-value=0.03) and higher grades of morphological changes- abnormal nuclear morphology (p-value=0.002) and Pseudo-Pelger-Huët anomaly in neutrophils (p-value=0.029), plasmacytoid lymphocytes (p-value=0.03), cytoplasmic granularity and atypical lymphocytes (p-value=0.04). Monocytes showed large coalescent vacuoles and cytoplasmic granules (p-value=0.03). Though present in non severe category (n=61), they were proportionately of lesser grades. Conclusion: Viral cytopathic effects in WBC cell lines on peripheral smear had significant clinical implications on disease severity, undermining need for a comprehensive study of viral induced morphological changes in hospitalised COVID-19 patients.

Study of Morphological Spectrum of Peripheral Blood Smear Changes in Coronavirus Disease 2019 (COVID-19) Positive Patients and its Correlation with Clinical Severity

Introduction: Peripheral blood changes in Coronavirus disease 19(COVID-19) are diverse and have been reported in literature in theform of brief communications and case series with relatively smallersample size and with a handful of studies showing associationbetween peripheral blood smear (PBS) and clinical severity of thedisease.Aims &Objectives: To highlight the numerical and morphologicalchanges in COVID-19 patients and to compare the same in IntensiveCare Unit (ICU) and non-ICU settings as well as between COVID-19survivors and deceased patients.Materials &Methods: This cross-sectional study included 80COVID-19 positive (41 ICU and 39 non-ICU) patients and 32COVID-19 negative ICU patients, done in Department of Pathology,ABVIMS &Dr RML Hospital, New Delhi from December 2020 toFebruary 2021. Complete blood counts (CBC) and PBS findings werestudied and scored by two pathologists blindfoldedly.Result: Among CBC parameters, absolute lymphocyte count (ALC)and absolute eosinophil count (AEC) were significantly lower inCOVID-19 positive cases as compared to COVID-19 negative group(p = 0.001 &p = 0.001). On PBS, COVID-19 positive group showedsignificant left myeloid shift (p = 0.021), Dohle bodies (p = 0.025)with significant prominence of acquired pseudo pelger-huet anomaly,ring shaped neutrophils, monolobulate neutrophils and plasmacytoidlymphocytes as compared to control group (p = 0.000, p = 0.009,p = 0.046 &p = 0.011 resp). The overall mean White blood cell(WBC) counts were higher in COVID-19 positive ICU patients ascompared to non-ICU COVID positive patients with significant shiftto left (p = 0.017). Ring shaped neutrophils, monocyte vacuolationand large granular lymphocyte (LGL) were significantly higher inCOVID-19 positive ICU patients as compared to non-ICU patients(p = 0.007, p = 0.008 &p = 0.004 resp). Deceased group (14/39 ICUCOVID positive cases) showed significantly high WBC count(p = 0.018) with marked neutrophilia (p = 0.024) and toxic granulation (p = 0.01) and prominence of monocyte vacuolization, ringshaped neutrophils, large granular lymphocytes and reactive lymphocytes as compared to survivor.Conclusions: Morphological parameters like myeloid left shift, ringshaped neutrophils, monocyte vacuolation, LGLs and reactive lymphocytes emerged as highly sensitive markers of COVID-19 diseaseseverity. Therefore, serial CBC with comprehensive PBS analysisshould be done in every newly diagnosed hospitalized COVID-19patients to potentially predicts the course of disease and its clinicaloutcome.