COVID-19 in tobacco users.

Smoking is a significant social problem threatening the population's health, especially during the coronavirus pandemic. Due to the problem's urgency, we present a clinical case of SARS-CoV-2 infection in a patient with 10 years of smoking and concomitant chronic obstructive pulmonary disease (chronic bronchitis and peribronchial pneumosclerosis). Patient L.K., 42 years old, on 13.10.2022, was hospitalized for several hours at the Emergency Hospital of the Ministry of Health of Chuvashia (Cheboksary) with a severe new coronavirus infection. Secondary diagnosis: Chronic obstructive pulmonary disease Case history: for about two to three weeks, the patient noted an increase in body temperature to 37.2-37.4 degreeC and a cough. He has smoked for about 10 years, 1 pack per day. Computed tomography showed signs of bilateral COVID-associated pneumonitis, alveolitis with 85% involvement and consolidation sites, signs of chronic bronchitis, and peribronchial pneumosclerosis. The diagnosis of COVID-19 was confirmed by a polymerase chain reaction in a nasopharyngeal smear. The NEWS2 score was 9. After the treatment started, the patient died. Histological examination showed perivascular sclerosis, peribronchial pneumosclerosis, atrophic changes in the ciliated epithelium, and structural and functional alteration of the bronchial mucosa. In addition, areas of hemorrhage and inflammatory infiltrate in the bronchial wall were found. Coronavirus is known not to cause bronchitis but bronchiolitis. In the presented case, the patient showed signs of transition of bronchitis to the acute stage. Therefore, it can be assumed that the coronavirus acts as a complicating factor. In addition to the described changes, signs of viral interstitial pneumonia, pulmonary edema, and early development of acute respiratory distress syndrome were identified.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

Maxillary osteomyelitis secondary to mucormycosis, a sequel of COVID-19: a clinical case report

Introduction: One of the consequences of COVID-19 is the incidence of mucormycosis in the jaws and subsequent osteomyelitis in patients with undiagnosed or uncontrolled comorbidities, such as diabetes mellitus and associated immunosuppression. Case Report: A 52-year-old male patient with a history of COVID-19 two months ago presented a painful ulcerative lesion of insidious onset in the palatal raphe measuring approximately 2 mm. He referred to numbness of the palatal region of one month of evolution. During the physical examination, purulent content, multiple pustules in the anterior maxillary buccal mucosa, and mobility of upper anterior teeth were observed. The CT revealed isodense bilateral images in maxillary and ethmoidal sinuses, bone sequestrations, and partial loss of anterior vestibular cortical bone. Laboratory tests revealed no abnormality, except for HbH1c: 10.2gr/dl. The patient was hospitalized for control of newly diagnosed diabetes mellitus. Maxillary incisional biopsy was performed, and microscopic analysis showed a mixed inflammatory infiltrate, fibrin deposits with eosinophilic and birefringent ribbon-like hyphae, branched at right angles, compatible with maxillary osteomyelitis secondary to mucormycosis. The treatment started with antifungal and intravenous antibiotics, followed by surgical cleaning under general anesthesia. The patient progressed favorably. Conclusion(s): Immunosuppression resulting from COVID-19 and/or uncontrolled systemic diseases can condition the appearance of rare opportunistic microorganisms causing infections such as mucormycosis. Early diagnosis and treatment make a difference in the morbidity and mortality of patients.

ECMO in acute fulminant myocarditis in pediatrics

Objectives: To describe our experience in ECMO for acute myocarditis Methods: Descriptive, retrospective study (2018-2022) of a cohort of 8 patients < 16 years with acute myocarditis who were assisted on ECMO. Result(s): 8 patients were collected, (6 females), with a mean age 7;8 years [range 0;1-13;8]. In 7/8, the reason for cannulation was hemodynamic instability refractory to medical treatment, with a mean inotropic score of 70 [range 10-122]. Sixty-two percent presented cardiorespiratory arrest prior to cannulation and 2 of them needed ECRP. The mean precannulation troponin level was 1498 ng/ml [range 89-6212]. Primary transport was performed in 4 patients. ECMO was peripheral veno-arterial in 100%, jugulo-carotid in 2/8 and femoro-femoral in 6/8. All patients underwent atrioseptostomy. They received treatment with levosimendan, immunoglobulins, corticoids and carnitine. In 4 acute infectious etiology was confirmed (parvovirus, influenza and SARSCoV2), another one was due to PIMS-TS and in 3 no etiology was found. Six patients underwent myocardial biopsy and 5 of them showed inflammatory infiltrates. The mean time on ECMO was 8 days [range 3-14], 2 of them requiring 2 ECMO courses. The mean length of PICU stay was 21 days [range 10-50]. Two were transferred to a heart transplant center. The main complications were arterial hypertension (88%), bleeding (63%), neurological (50%), arrhythmias (38%), coagulopathy (38%) and infectious (38%). One patient required renal replacement therapy. 1 patient died, 2 had moderate neurological sequels. Conclusion(s): ECMO is a therapeutic option in patients with fulminant myocarditis refractory to medical treatment and may help improve their prognosis.

Is It Cancer Hepatic Inflammatory Pseudotumor: An Important Hepatic Mass Differential

Introduction: Hepatic inflammatory pseudotumor (HIP), albeit rare, is an important pathology to be included in differentials for hepatic masses. The benign nature and treatment of this disease process should be considered especially in comparison to malignant hepatic processes. Case Description/Methods: A 66-year-old male with pre-existing history of compensated Hepatitis C cirrhosis status post direct-acting antivirals with sustained virologic response presented in shock after a syncopal episode. Initial work up revealed leukocytosis, thrombocytopenia, acute renal injury, elevated liver enzymes, and COVID-19 positive test. Patient underwent initial liver ultrasound revealing intrahepatic and extrahepatic biliary ductal dilation. Subsequent MRCP demonstrated diffuse thickening of intra and extra hepatic bile ducts suggestive of cholangitis and several hepatic masses concerning for abscesses versus possible metastatic cholangiocarcinoma. Patient improved symptomatically with antibiotics and supportive care. A liver biopsy was performed with pathology showing lymphoplasmacytic inflammation and fibroblastic infiltration suggestive of hepatic inflammatory pseudotumor. A repeat MRCP one week later showed interval decrease in size of liver lesions and repeat liver function tests also showed improvement. Patient was discharged on a course of ciprofloxacin and metronidazole. Patient had repeat MRCP 3 months after discharge, with further significant improvement in size of liver lesions. After multi-disciplinary discussion the plan was for further surveillance with imaging and labs in 2 months. Discussion(s): Inflammatory pseudotumors are benign and non-neoplastic lesions that can occur in any organ. They can appear as a malignant lesion when they arise in the liver and an accurate identification can allow for conservative management and prevent unnecessary invasive procedures. Hepatic inflammatory pseudotumors are often seen with concomitant infection or inflammatory processes. Liver biopsies distinguish these tumors from other malignant processes as they demonstrate a characteristic dense inflammatory infiltrate interspersed in stroma of interlacing bundles of myofibroblasts. This case highlights the importance of maintaining HIP on the differential diagnosis. (Figure Presented).

COVID-19 in tobacco users.

Smoking is a significant social problem threatening the population's health, especially during the coronavirus pandemic. Due to the problem's urgency, we present a clinical case of SARS-CoV-2 infection in a patient with 10 years of smoking and concomitant chronic obstructive pulmonary disease (chronic bronchitis and peribronchial pneumosclerosis). Patient L.K., 42 years old, on 13.10.2022, was hospitalized for several hours at the Emergency Hospital of the Ministry of Health of Chuvashia (Cheboksary) with a severe new coronavirus infection. Secondary diagnosis: Chronic obstructive pulmonary disease Case history: for about two to three weeks, the patient noted an increase in body temperature to 37.2-37.4 degreeC and a cough. He has smoked for about 10 years, 1 pack per day. Computed tomography showed signs of bilateral COVID-associated pneumonitis, alveolitis with 85% involvement and consolidation sites, signs of chronic bronchitis, and peribronchial pneumosclerosis. The diagnosis of COVID-19 was confirmed by a polymerase chain reaction in a nasopharyngeal smear. The NEWS2 score was 9. After the treatment started, the patient died. Histological examination showed perivascular sclerosis, peribronchial pneumosclerosis, atrophic changes in the ciliated epithelium, and structural and functional alteration of the bronchial mucosa. In addition, areas of hemorrhage and inflammatory infiltrate in the bronchial wall were found. Coronavirus is known not to cause bronchitis but bronchiolitis. In the presented case, the patient showed signs of transition of bronchitis to the acute stage. Therefore, it can be assumed that the coronavirus acts as a complicating factor. In addition to the described changes, signs of viral interstitial pneumonia, pulmonary edema, and early development of acute respiratory distress syndrome were identified.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

Uncontrolled Acromegaly Resulting in the Need for LVAD as Bridge to Heart Transplant

Introduction: Acromegaly is an uncommon pituitary disorder with an incidence of six per million persons. While hypertension is often encountered in these patients, heart failure rarely is seen with an incidence rate under 10%. We describe a case of an individual who was diagnosed with acromegaly after an acute exacerbation of heart failure with subsequent management requiring an LVAD to perform Transsphenoidal Surgery (TSS). Case Description: 37-year-old male otherwise healthy initially presented to an emergency room and was found to be in acute heart failure exacerbation. Concerning acromegaly features included macrognathia, enlarged hands and feet, swollen phalanges, widened spacing of teeth, and frontal bossing. IGF-1 level was found 455 ng/mL. MRI showed a 10mm macroadenoma. A right heart catheterization showed elevated filling pressures. Cardiac MRI showed no defects or enhancement. Endomyocardial biopsy showed no inflammatory infiltrates or evidence of infiltrative diseases. Patient had an ejection fraction of 15% corroborated by cardiac MRI along with the presence of aortic root dilatation and mitral regurgitation. The patient started on 0.5mg of Cabergoline twice weekly and 120mg weekly Lanreotide injections. Patient stabilized with plans for further close monitoring and outpatient neurosurgical evaluation. The COVID-19 pandemic and insurance gaps led the patient to spend two years off his medicines and he was unable to be seen by his medical team. Patient was seen by our system after recurrent hospitalizations for heart failure at our sister hospital, AICD was unable to be placed due to the patient's anatomy, he was placed on wearable cardiac defibrillator and required milrinone infusion for progression to end-stage heart failure with cardiac cachexia. At our institution, the patient was evaluated for Orthotopic Heart Transplant (OHT) but due to active GH secreting macroadenoma there was concern for OHT failure without TSS. Decision was made to utilize LVAD as Bridge-to-Transplant for OHT so the patient could be stabilized and safely undergo TSS. The patient tolerated surgeries well and is currently on the active transplant list. Discussion(s): Heart failure is an uncommon presentation of severe acromegaly requiring multidisciplinary management. We describe a case of a patient who initially presented with heart failure too unstable for surgery. Due to the COVID-19 pandemic the patient's disease progressed resulting in end-stage heart failure requiring LVAD placement for further treatment. We would like to draw attention to the use of LVAD placement in acromegalic patients who develop severe cardiovascular disease who are not candidates for OHT.Copyright © 2023

Leukocytoclastic vasculitis following immunization with COVID-19 vaccine

Case report Introduction: Vaccines have been recognized as agents associated with development of different forms of vasculitis. We describe the case of a leukocytoclastic vasculitis which developed after immunization with inactivated COVID-19 vaccine. Case presentation: A 68-years old female patient presented with painful purpuric papules and plaques, and areas of necrosis, dominantly localized on her feet (Figure 1), developing 12 days after she received first dose of inactivated COVID-19 vaccine (BBIBP Cor-V). There were no other symptoms except mild fatigue and low-grade temperature of 37.3degreeC. Skin biopsy showed damaged vessel wall with perivascular, neutrophilic inflammatory infiltrate, leucocytoclasia and erythrocytes extravasation (Figure 2). Thorough work-up, including broad immunoserological and virological analysis didn't reveal any other potential trigger. Three months before vaccination the patient recovered from COVID-19 pneumonia. After the four weeks course of prednisone (initially 20 mg/day) with tapering a complete resolution of skin changes was achieved. The patient was followed for one year with no relapses. Conclusion(s): COVID-19 immunization should be considered as a potential trigger for development of cutaneous vasculitis.

Toxic epidermal necrolysis as a result of chlorthalidone and cyclophosphamide combination

Case report Introduction: Toxic epidermal necrolysis (TEN), is an immune-mediated disease characterized by severe mucocutaneous symptoms and is the result of an inflammatory response that leads to keratinocyte necrosis and perivascular lymphocyte infiltration, mostly drug-related. Case report: A 35-year- old male, with a history of recently diagnosed systemic lupus under treatment with prednisone, hydroxychloroquine, mycophenolate and cotrimoxazole forte evolves with persistent proteinuria, it is decided to add losartan, chlorthalidone and atorvastatin. Nevertheless despite immunosuppression, proteinuria and skin involvement persisted, so mycophenolate was suspended and a bolus of cyclophosphamide 1 g was administered. Eight weeks after adjusting treatment, the patient went to the emergency department due to a confluent, pruritic, maculopapular rash with blistering lesions on the trunk, upper limbs, face, and oral mucosa, associated with fever over 38degreeC, that evolved during one week. On admission, the following was confirmed: confluent erythematous macular exanthem associated with multiple flaccid blisters on the chest, upper limbs and neck, Nikolsky's sign (+), keratoconjunctivitis and dryness on the lips. Admission tests included complete blood count with no leukocytosis or eosinophilia, ESR 29 mm/hr, C-RP 19.8 mg/L, no liver profile abnormalities, creatinine 0.8 mg/dl, and urine test with proteinuria 300 mg/dl. Negative infectious study for mycoplasma, herpes 6 virus, cytomegalovirus, Epstein barr virus, hepatitis A, B, C, E and SARS-COV2 virus. Due to severe mucosal skin involvement, TEN/SJS was suspected v/s (TEN)-like Lupus presentation, drugs used prior to admission (chlorthalidone, losartan, atorvastatin) were discontinued, and treatment was started with Hydrocortisone 100 mg every 8 hours IV, Immunoglobulin 2 g/kg daily IV for 4 days, plus skin and mucous membrane care. Patient had a favorable evolution, with resolution of skin and mucosal lesions and no signs of infection. Skin biopsy showed necrotic epidermis, necrotic basal keratinocytes, and sparse lymphocytic inflammatory infiltrate in the papillary dermis, consistent with erythema multiforme/toxic epidermal necrolysis. Conclusion(s): Extensive mucosal involvement is one of the cardinal signs of the presentation of SJS/ETN and given its severity, a high index of suspicion is important with the consequent suspension of suspected drugs and support management for a favorable evolution. In this case the suspected culprit drug was the combination of cyclophosphamide and chlorthalidone, due to reports of increased toxicity of cyclophosphamide in combination with diuretic drugs.

Acute exantematic pustulosis generalized by meropenem, differential diagnosis with COVID

Case report We present the case of a 63-year- old man with two consecutive admissions, due to COVID19 infection and subsequent bacterial superinfection. Three days after the second admission (04/28), and 43 days from the beginning of the infection an assessment by dermatology and allergology is then requested. The patient had generalized erythematous maculopapular rash in the trunk, back, groin and limbs. On the left side and back, pustular lesions not focused on follicles were also added, with a fever of 37.7degreeC. There were no oral and genital lesions. No psoriasis. The drugs used during the present and previous admissions were reviewed. Previous admission (04/04-22/ 20): Linezolid, ciprofloxacin, meropenem 04/13-22, piperacillin/tazobactam, hydroxychloroquine, azithromycin, ceftriaxone. Upon discharge amoxicillin/acid clavulanic. Present admission (04/25) Cutaneous reaction 04/28. 04/25: meropenem, paracetamol, enoxaparin, insulin, omeprazole, venlafaxine. 04/26: Darbepoetin, furosemide, mycophenolate in single dose. 04/27: Linezolid, macrogol, Clopidogrel, Magnesium, Calcitriol. Medical records: DM type 2, liver transplantation due to HCV cirrhosis, HCV recurrence, uninodular hepatocarcinoma, advanced CKD, secondary hyperparathyroidism, multiple neurological antecedents. We performed a detailed study. We hypothesized with a pharmagological/ drug reaction with several drugs possibly involved and our main suspicion was an allergic reaction to beta-lactams. Biopsy: Subcorneal pustules, basal spongiosis and presence in the superficial dermis of edema and an inflammatory infiltrate with abundant neutrophils. No fungi. Findings compatible with clinical diagnosis of generalized acute exanthematic pustulosis (PEGA). Immunohistochemical study Covid19. (Jimenez Diaz Foundation) Finely granular positivity in endothelium and more coarse in sweaty epithelium. Neutrophilic superficial inflammatory component with presumably spure staining. ACe-2 (positive external control) is not detected. The patient presents a EuroSCAR score of 9, sum of the clinic and the pathological anatomy, and therefore defined diagnosis. Clinical diagnosis: PEGA secondary to meropenem. Conclusion(s): We present the case of a PEGA by meropenem, not very often described in the literature. We highlight the importance of differential diagnosis with viral infections. Skin tests, especially epicutaneous tests, are key to the diagnosis. (Figure Presented).

Phototherapy to treat a COVID-19 vaccine reaction

A 59-year-old man presented with a widespread morbilliform rash after receiving the second dose of the Pfizer-BioNTech COVID-19 mRNA vaccine. He had no significant medical history and no known allergies. He did not take any regular medication. He developed pruritus without rash 4 h after his first vaccine. This resolved after 10 days without intervention. One day after his second dose, he developed an extensive pruritic morbilliform eruption on his trunk and limbs, affecting 35% of his body surface area. with no mucous membrane involvement. The rash persisted for 4 weeks after his second vaccination and he was referred to dermatology. Eosinophils were raised at 0.54 and liver function tests were normal. Antinuclear antibodies and extractable nuclear antigen were negative. Complement levels were normal. Histology showed mild epidermal acanthosis, spongiosis and subcorneal vesicles. Within the superficial to mid-dermis, there was a mixed chronic inflammatory infiltrate comprising lymphocytes, plasma cells, neutrophils and numerous eosinophils. Direct immunofluorescence was negative. He received a tapering dose of oral prednisolone with mometasone topically. Despite substantial improvement with this regimen, his rash began to worsen 2 days following discontinuation of oral prednisolone. He was still using daily mometasone on cessation of oral steroids. He was trialled on oral doxycycline for 1 month, which led to a marked improvement in the morbilliform rash. Despite improvement in the rash, the patient reported ongoing intense daily pruritus which was having a marked impact on his quality of life. He has commenced on narrowband ultraviolet B (UVB) phototherapy to treat his persistent pruritis, with good effect to date. Morbilliform eruptions have been reported as a cutaneous manifestation of COVID-19 and as a side-effect of mRNA vaccines. Proposed mechanisms for the development of skin rashes post-mRNA vaccines include viral protein expression following vaccination, prior infection with COVID-19 causing cross-reaction with the mRNA vaccine encoded antigen and vaccine components acting as haptens inducing a T helper 2 inflammatory reaction characterized by interleukin (IL)-4 and IL-13 expression. Drug-induced maculopapular eruptions typically resolve within 7-14 days on withdrawal of the culprit medication. The persistent nature in our patient may imply a complex immune response. The use of phototherapy to treat inflammatory dermatoses and pruritic conditions such as nodular prurigo is well described. The antipruritic effect of phototherapy is thought to work via modulation of both the neural pathways involved in itch and local immune cells in the skin. Our case highlights that phototherapy can be used in the treatment of cutaneous side-effects that arise after COVID-19 vaccines. To the best of our knowledge, this case is one of the first to use narrowband UVB phototherapy to treat a cutaneous side-effect of an mRNA vaccine.

Perniosis: a rare cutaneous manifestation of paroxysmal nocturnal haemoglobinuria

Perniosis is a vaso-occlusive phenomenon that features the formation of discrete erythematous papules, macules, nodules or patches. Perniotic lesions are induced by the cold and are symptomatic in terms of burning, pain or itching. Secondary complications such as overlying infections and ulceration may occur (Takci Z, Vahaboglu G, Eksioglu H. Epidemiological patterns of perniosis, and its association with systemic disorder. Clin Exp Dermatol 2012;37: 844-9). While most cases of perniosis are idiopathic, studies have shown a link between secondary perniosis, connective tissue diseases and haematological disorders. Paroxysmal nocturnal haemoglobinuria (PNH) is a haematological aberrant stem cell disorder. It is a very rare condition (1-1 5 cases per million population) and results in the death of approximately 50% of affected individuals as a result of thrombotic complications. Cutaneous sequelae are uncommon and may present as purpura due to dermal vein thrombosis (Zhao H, Shattil S. Cutaneous thrombosis in PNH. Blood 2013;122: 3249). To date, there have been no previously reported cases of perniosis as a cutaneous manifestation of PNH. A 42-year-old man, with a background of PNH and aplastic anaemia, presented with recurrent painful, erythematous macules and blisters along the palmar and plantar aspects of his fingers and toes. These lesions occurred over 4 years previously, coinciding with the diagnosis of PNH and aplastic anaemia. Physical examination revealed a solitary blistering lesion on the palmar aspect of his third right finger. In addition, there were multiple erythematous macules on the plantar aspect of the first and second toe of his left foot. A biopsy was performed. An autoimmune screen and antibodies for COVID-19 were all negative. Histopathological findings showed epidermal blister formation with the presence of some apoptotic keratinocytes admixed with superficial chronic perivascular inflammatory infiltrate. The inflammatory infiltrate was predominantly chronic lymphocytic and locally involved perieccrine glands noted to be underlying the blister formation, consistent with perniosis. The patient is currently awaiting treatment with eculizumab. This is a case of perniosis occurring as a cutaneous manifestation of PNH. Perniosis typically requires investigation for connective tissue diseases;however, we also warn dermatologists that perniosis could be a presenting feature of underlying paroxysmal nocturnal haemoglobinuria, a rare, life-threatening condition with a high mortality rate related to thromboembolism. This case highlights an interesting and previously unreported cutaneous manifestation of PNH.

Isolated tracheobronchial mucormycosis: Report of a case and systematic review of literature

Background: Isolated tracheobronchial mucormycosis (ITBM) is an uncommonly reported entity. Herein, we report a case of ITBM following coronavirus disease 2019 (COVID-19) and perform a systematic review of the literature. Case description and systematic review: A 45-year-old gentleman with poorly controlled diabetes mellitus presented with cough, streaky haemoptysis, and hoarseness of voice 2 weeks after mild COVID-19 illness. Computed tomography and flexible bronchoscopy suggested the presence of a tracheal mass, which was spontaneously expectorated. Histopathological examination of the mass confirmed invasive ITBM. The patient had complete clinical and radiological resolution with glycaemic control, posaconazole, and inhaled amphotericin B (8 weeks). Our systematic review of the literature identified 25 additional cases of isolated airway invasive mucormycosis. The median age of the 26 subjects (58.3% men) was 46 years. Diabetes mellitus (79.2%) was the most common risk factor. Uncommon conditions such as anastomosis site mucormycosis (in two lung transplant recipients), post-viral illness (post-COVID-19 [n = 3], and influenza [n = 1]), and post-intubation mucormycosis (n = 1) were noted in a few. Three patients died before treatment initiation. Systemic antifungals were used in most patients (commonly amphotericin B). Inhalation (5/26;19.2%) or bronchoscopic instillation (1/26;3.8%) of amphotericin B and surgery (6/26;23.1%) were performed in some patients. The case-fatality rate was 50%, primarily attributed to massive haemoptysis. Conclusion: Isolated tracheobronchial mucormycosis is a rare disease. Bronchoscopy helps in early diagnosis. Management with antifungals and control of risk factors is required since surgery may not be feasible. © 2022 Wiley-VCH GmbH.

A Rare Case of Granulomatous Interstitial Nephritis in a Patient With COVID-19-Associated Collapsing Glomerulopathy

Introduction: AKI in patients with COVID-19 is common. Among glomerular pathologies in COVID 19, COVID 19 Associated Collapsing Glomerulopathy (COVAN) remains the most common pattern of injury. AIN is a less common finding in patients with COVID-19. Reports of a subtype of AIN, granulomatous interstitial nephritis (GIN), among COVID-19 patients, are rare and have not been reported in association with COVAN. Here, we report a case of COVAN associated with severe GIN Case Description: A 52YOM who presented with fever and fatigue. The physical exam was remarkable. The patient tested positive for COVID-19 and was found to have oliguric AKI with a creatinine of 9.6 mg/dl and nephrotic range proteinuria. Therefore iHD was initiated. Serologies and infection studies were negative. Fungal serologies were negative. A kidney biopsy revealed up to 32 glomeruli, four of which were globally sclerotic. Up to four glomeruli had features of glomerular collapse. The interstitium showed severe, diffuse edematous change with inflammatory infiltrates and focal interstitial granulomas. EM showed extensive foot process effacement and multiple TRI. Additional stains were negative. After the biopsy results returned, the patient was started on high-dose steroid. He experienced side effects with the high dose and therefore was transitioned to an every other day regimen. Losartan was added and prednisone taper was started. He was doing very well clinically at the last visit with resolving AKI and proteinuria Discussion: We have presented a rare case of GIN in a patient with COVAN. With negative infectious and autoimmune evaluation, it is possible the GIN was secondary to drug exposure and/or potentiated by the inflammatory mileu of COVID-19 infection. Even several years into the pandemic, we continue to find new kidney pathology among COVID-19. Kidney biopsy was absolutely necessary in this case and informed a dedicated treatment plan that allowed a remarkable recovery of kidney function.

DYSPNEIC AFTER EVERY COVID-19 SHOT: SUSPECTED BNT162B2 MRNA VACCINE-RELATED, DRUG-INDUCED PULMONARY EOSINOPHILIA

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: Eosinophilia is the most commonly reported adverse event following administration of the Pfizer/BioNTech vaccine, accounting for 237 of 372 events (63.7%). Eosinophilic pneumonia has been described noted in 3 of all reported cases. CASE PRESENTATION: We present the case of a 73 year-old male presented to his PCP with a 3 week history of nonproductive cough and wheezing. He completed a 2-shot series of BNT162b2 mRNA (Pfizer/BioNTech) COVID vaccine 1 week prior to symptom onset. He had no history of respiratory symptoms, smoking, sick contacts, recent travel, chemical or biological exposures. On presentation, he was afebrile, tachycardic and required 3LPM supplemental oxygen to maintain peripheral oxygen saturation (SpO2) above 94%. Laboratory findings noted leukocytosis (13,200/mL) and eosinophilia at 5% (Absolute Eosinophil Count (AEC): 580 cells/L). Respiratory viral panel, procalcitonin, ESR and D-dimer were negative. Chest CT scan was unremarkable. He was treated with azithromycin, prednisone and inhaled bronchodilators with improvement in hypoxia. 2 weeks later, he reported intermittent dyspnea during a pulmonary clinic visit. Pulmonary function testing was normal (FEV1/FVC: 76%;FVC: 3.67L (90% predicted);FEV1: 2.80L (88% predicted). IgE level was normal and eosinophilia had resolved. 6 months after initial symptom onset, the patient received his third BNT162b2 mRNA vaccine dose. 2 weeks after vaccination, he presented to the ED with severe dyspnea, wheezing and cough with yellow sputum. He also noted a new itchy, erythematous bilateral forearm rash and painless oral ulcers. On exam, he was afebrile, tachypneic with SpO2 of 93% on 4LPM supplemental oxygen and audibly wheezing with a prolonged expiratory phase. Laboratory studies noted elevated creatinine and leukocytosis (23,100/mL) with marked eosinophilia (29.5 %, AEC: 6814 cells/L). Chest CT scan revealed a 2 cm rounded ground-glass opacity in the right upper lobe. (Figure 1.) Further workup revealed a weakly positive antihistone antibody (1:4 titer). IgE, ANA, ANCA, SS-A/B, anti-CCP, and complement levels were normal. Intravenous methylprednisolone treatment was initiated with rapid improvement in dyspnea, eosinophilia and renal function. A transbronchial biopsy (Figure 2.) of the RUL lung lesion revealed organizing pneumonia with mixed inflammatory infiltrate. Bronchoalveolar lavage analysis revealed elevated WBC (432 cells/L) with neutrophilic predominance (85%). Patient was discharged home on a prednisone taper with resolution of symptoms. DISCUSSION: Subsequent allergy work up did not indicate any apparent etiology of hypereosinophilia. Testing for strongyloides, coccidiosis and aspergillosis were also negative. A final diagnosis of BNT162b2 mRNA vaccine related pulmonary eosinophilia was made. CONCLUSIONS: Additional study is warranted into eosinophilic disease associated with the BNT162b2 mRNA vaccine. Reference #1: 1. United States Department of Health and Human Services (DHHS), Public Health Service (PHS), Centers for Disease Control (CDC) / Food and Drug Administration (FDA), Vaccine Adverse Event Reporting System (VAERS) 1990 - 03/11/2022, CDC WONDER On-line Database. Accessed at http://wonder.cdc.gov/vaers.html on Mar 11, 2022 1:18:37 PM DISCLOSURES: No relevant relationships by Matthew Haltom No relevant relationships by Nikky Keer No relevant relationships by Thekrayat Khader No relevant relationships by Muthiah Muthiah

LIVER INJURY ASSOCIATED WITH TURMERIC&≤x2013;A GROWING PROBLEM: NINE CASES FROM THE DRUG-INDUCED LIVER INJURY NETWORK [DILIN]

BACKGROUND: Turmeric (curcumin) is a commonly used over-the-counter herbal product whose uses include diarrhea, arthritis, cancer and even COVID-19. Recently turmeric has been implicated in cases of clinically apparent liver injury with jaundice. The aim of this case series is to describe the clinical, histologic and human leukocyte antigen (HLA) associations of turmeric-associated hepatotoxicity as seen in the U.S. Drug Induced Liver Injury Network (DILIN) Prospective Study. METHODS: All adjudicated cases enrolled in DILIN between 2003-2020 with turmeric as an implicated product were reviewed. Causality was assessed using a 5-point expert opinion score. Available products were collected and analyzed for the presence of turmeric using ultra-high-performance liquid chromatography. Genetic analyses included HLA sequencing. RESULTS: Of 1697 cases of drug-induced liver injury judged to be definite, highly likely or probable (high confidence), nine (0.5%) were attributed to turmeric, all of which were enrolled since 2012, and 6 since 2017 (Figure). The 9 cases included 7 women, 8 whites, with a mean age of 51 years (range, 35-62 years) and BMI 25 kg/m2 (range, 15-40). Seven patients used alcohol, but none to excess, and none had underlying liver disease. Turmeric was used for an average of 102 days before onset of injury (range, 30-425 days). Initial mean ALT was 1179 U/L (range, 328-2245), ALP 211 U/L (41-441), total bilirubin 5.9 mg/dL (1.2-10.8), and INR 1.0 (0.9-1.2). Six patients developed jaundice, and serum bilirubin peaked at 9.6 mg/dL (0.8-26), and INR 2.3 (1.0- 9.7). Liver injury was hepatocellular in 8 patients (mean R = 22). Five patients had elevated antinuclear antibody (ANA) titer and two anti-smooth muscle (ASM) antibody, but none were treated with corticosteroids. Liver biopsy in 5 patients showed portal and lobular mixed inflammatory infiltrates with lymphocytes and eosinophils typical of drug-induced liver injury. Five patients were hospitalized, and one patient died of acute liver failure. Chemical analysis confirmed the presence of turmeric in all 7 products analyzed;3 also contained piperine (black pepper), and none contained green tea. Of 7 patients with HLA typing available, 4 carried HLA-B*35:01, a class I HLA allele previously implicated in both green tea and Polygonum multiflorum hepatotoxicity. CONCLUSION: Liver injury due to turmeric appears to be increasing, perhaps, reflecting usage patterns or increased combination with black pepper, which increases its absorption. Turmeric liver injury, similar to that caused by other polyphenolic herbal products, is typically hepatocellular, with a latency of 1 to 6 months, and is linked to HLA-B*35:01. While most cases are self-limited, the injury can be severe and result in death or liver transplantation.

A Rare Case of Eltrombopag-Induced Pneumonitis

Introduction Immune thrombocytopenia (ITP) is an acquired thrombocytopenia due to autoantibodies. Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) used as a second-line agent in the setting of persistent or chronic ITP. Potential severe adverse effects include hepatotoxicity, thromboembolism, and increased risk of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Upper respiratory infections and pharyngitis have also been described, but to our knowledge, no known cases of eltrombopag-induced pneumonitis have been reported to date. Case Presentation We present a 68-year-old male with a history of recent onset ITP, stage IV mantle cell lymphoma (in remission), and Pneumocystis pneumonia who was initiated on eltrombopag 11 days prior to admission for ITP refractory to corticosteroid therapy. Three weeks prior to admission, the patient underwent a bone marrow biopsy without evidence of monoclonal B cells or immunophenotypically abnormal T cell populations. Following initiation of eltrombopag, the patient had progressive dyspnea on exertion associated with subjective fevers and chills requiring hospitalization. Oxygen saturation was 88% on room air with exam notable for coarse crackles to the bilateral lung bases. CT angiogram of the chest revealed bilateral pulmonary emphysema, ground glass opacities, and bilateral bronchiectasis most pronounced in the lower lobes (Figure 1). No pulmonary embolism or mediastinal adenopathy was identified. Cytomegalovirus DNA, aspergillus antigen, and COVID-19 NAAT testing were negative. A respiratory viral panel was positive for Rhinovirus. Bronchoalveolar lavage (BAL) and right middle lobe lung parenchymal biopsy were subsequently performed. Pathology demonstrated focal intra-alveolar organization and fibroblast plugs, interstitial fibrosis, pneumocyte hyperplasia, and mixed (predominantly chronic) inflammatory infiltrate (Figure 2a & 2b). BAL was negative for malignant cells. Pneumocystis jirovecii DNA was detected, but < 250 copies/mL were identified and thus was thought to be less likely contributing to the disease process.Given the suspicion for eltrombopag-induced pneumonitis, the patient was initiated on high-dose corticosteroid therapy with a slow taper over the span of several weeks. Following initiation of corticosteroids, the patient was noted to have gradual improvement in his respiratory status. The patient was ultimately discharged on room air 1 month later due to other hematologic complications necessitating a prolonged hospital stay. Discussion The exact mechanism of eltrombopag-induced pneumonitis is unclear, although we postulate that it is related to an exaggerated immune response involving T-cell homeostasis resulting in alveolarcapillary permeability, inflammation, and fibrosis. Suspicion for eltrombopag-induced pneumonitis should prompt initiation of early corticosteroid therapy to prevent acute and chronic complications of pneumonitis. (Figure Presented).

Molecular Methods in the Identification of Pulmonary Pathologic Traits of the SARS-CoV-2 Delta Variant at Autopsy

Background: The highly contagious Delta variant of COVID-19 accounts for more than 80% of SARS-CoV-2 cases in the fall of 2021. Our aim was to determine whether molecular methods for variant and lineage detection could be utilized at autopsy to examine pathologic findings of Delta variant as compared to non-Delta variant cases. Design: We evaluated the lungs from 20 decedents with death due to SARS-CoV-2 confirmed by antemortem nasopharyngeal RTPCR in July and August 2021 (Delta wave), as well as from 40 autopsy cases prior to February 2021 with death due to SARS-CoV- 2. The patient population included males and females, with an age range of 37-67 years in the Delta group, and 44-79 In the non- Delta group. The population demographic was considered at risk for death due to COVID-19, and only one decedent, with immunosuppression, was known to be vaccinated. Lung specimens were examined on H&E and with SARS-CoV-2 nucleocapsid immunostain (IHC). Results: The time from initial symptoms to death averaged 9 days within the Delta wave and 16 days in non-Delta cases. Steroids, anticoagulation, antibiotics, and monoclonal antibody infusion were frequently part of the clinical treatment of Delta wave cases. Notably, SARS-CoV-2 PCR of lung swabs at autopsy were positive in all but one case examined in the Delta variant group, and viral genome RNA sequencing from lung at autopsy confirmed Delta variant lineage. In both groups, gross features of the lungs included edema, while grossly identifiable thrombi were more commonly seen in non-Delta variant cases. Histologic examination revealed diffuse alveolar damage (DAD) in all cases, most commonly early stage DAD in Delta variant cases. SARS-CoV-2 IHC demonstrated patchy to strong positivity in the alveoli of the majority of Delta variant cases - a finding not frequently seen in non-Delta cases. Figure 1 - 15 Conclusions: Our study is the first to incorporate PCR and viral genome sequencing from the lung at autopsy to correlate the Delta variant wave with histopathologic findings - a technique that may be useful in identifying important pathologic features of future variants. While the finding of DAD remains the same across viral variants, the majority of Delta cases showed a significant presence of SARS-CoV-2 in the lung by IHC, with minimal inflammatory infiltrate and reduced thrombotic complication. Whether these findings are the result of a shorter time interval between disease onset and death, therapeutic intervention, or increased viral load remains to be determined.

Characteristic Histological and Molecular Findings in SARS-CoV-2-infected Placentas and its Impact on the Fetus. Study of 279 Cases from Pregnant Women Affected by COVID-19 during the Pandemic

Background: Placental pathology in pregnant women infected by SARS-CoV-2 has generated many reports with non-specific or contradictory results. The objective is to identify histological and molecular findings of infected placentas and its impact on the course of pregnancy. Design: Placentas from 279 women infected with SARS-CoV-2 during pregnancy were reviewed, 137 of them with active infection within 10 days prior to delivery and 142 with past infection beyond this period. Four fetal autopsies were submitted for pathological study. Placental and fetal infection was investigated by immunohistochemistry (IHC) in 279 cases, RT-PCR in 27 cases and in situ hybridization (ISH) in 5 cases. Significance of association between qualitative variables was tested by Fisher's exact test. Results: SARS-CoV-2 infection of placental tissues was demonstrated in 16/279 (5,7%) by IHQ (granular cytoplasmic villous trophoblast staining) and confirmed by ISH and RT-PCR (carried on 5 IHQ positive cases). All these 16 infected placentas showed diffuse (6/16) or focal (10/16) Trophoblast Damage (DTD/FTD) characterized by trophoblast necrosis with preserved villous stroma, collapse of the intervillous space, intervillous fibrinoid deposits, and variable polymorphous inflammatory infiltrates. Cases with DTD (>80% of the parenchyma affected) resulted in 5 stillbirth and 1 premature alive baby (27w) born after induction of labor for pathologic fetal non-stress test. In 4/5 deaths an autopsy was performed and infection of fetal tissues was not demonstrated by IHQ. The cases with FTD (<35% of the parenchyma affected) hadn't negative impact on the fetus. Correlation between placental infection and DTD/FTD had statistical significance (p<0,001). 15/16 placentas belonged to the group of pregnant women with active infection within 10 days prior delivery. Correlation between DTD/FTD and maternal active infection had statistical significance (p<0,002). Conclusions: Placentas infected by SARS-CoV2 has a characteristic histological pattern that we have defined as DTD or FTD, characterized by a predominant villous trophoblast necrosis, intervillous space collapse and variable degrees of mixed inflammation and intervillous fibrinoid deposition. DTD/FTD is an infrequent lesion observed in 5,7% of pregnant women affected by COVID-19 in our series. DTD can be the cause of fetal death due to placental insufficiency. In this study, vertical transmission of the virus to the fetus has not been demonstrated.

Histopathologic Pulmonary Involvement of COVID-19: A Comparative Study of SARS-CoV-2 Variants in Mouse Models

Background: A thorough understanding of the inflammatory reaction to SARS-CoV-2 variants, specifically the Delta and Alpha variants, can provide crucial insight into future treatment of individuals infected with these strains. Mice are an effective model for predicting the pathologic processes of these viruses in humans. Design: K18-hACE2 transgenic mice were raised either under normal conditions (control) or infected with either the Alpha (strain B.1.1.7) or Delta (B.1.617.2) variant of SARS-CoV-2, via intranasal challenge with 1000 PFU virus. Mice were then euthanized at days 2 and 6 post-challenge. Lung sections were used for pathological evaluation of H&E stained slides scanned using the Dynamyx software. Blood vessel cross sections were examined and the average number of marginating inflammatory cells per millimeter of vessel were quantified. Additionally, the percentage of total tissue area that was inflamed was calculated. Results: Our data indicates that the Delta variant elicits a strong lymphocytic immune response in the lungs. At two days postchallenge, Inflammation and margination of inflammatory cells could be appreciated in Delta infected mice, but not in Alpha infected mice. The inflammatory infiltrate was composed predominantly of lymphocytes and occasional histiocytes at 2 days. By day 6, marked perivascular inflammation and margination was appreciated, more prominently in Delta (36 lymphocytes per mm. of endothelium) than Alpha infected mice (22 lymphocytes per mm. endothelium) (p=0.022). At this time point, Alpha infected mice showed 4% involvement of pulmonary area by inflammation, compared to 20% for Delta infected mice (p=0.014). Conclusions: This study quantifies the lymphocytic immune response in the lungs to the Alpha and Delta variants of SARS-CoV-2 in mouse models. Both variants showed a lymphocyte predominant inflammatory response. However, the response was much more robust and severe in Delta infected mice compared to Alpha. The results support why the Delta variant is more virulent and fatal compared to Alpha. Ongoing longer term studies and effects in other organs are ongoing and will help to provide further insight into pathogenesis of long COVID-19.

HEMATOBIOCEMICAL AND HISTOPATHOLOGICAL STUDIES ON THE EFFECTS OF RAJ NIRWAN BATI (A NOVEL ALLOVEDIC DRUG) IN WISTAR RATS

Objective: To see the effects of Raj Nirwan Bati (RNB) on the hematobiochemical parameters, coagulation tests, and histopathological changes in the lungs, liver, kidneys and spleen and also to evaluate the immunomodulatory activity of RNBin Wistar rats. Methods: A total of 24 adult albino Wistar rats (of bodyweight 200-250 g) of either sex were divided into 3 groups. In the normal control group (n=8), no drug was administered and in the rest of the groups (A and B), RNB@ 26 mg/kg body weight./day and 260 mg/kg body weight/day respectively were administered orally for a period of 14 d. The blood samples were collected from the jugular vein at zero d (before drug administration) and after the 14th d of drug administration in both groups (A and B). The organ samples (lungs, liver, kidneys, and spleen) were collected after euthanizing the rats using Ketamine anesthesia overdose intraperitoneally (IP) after the 14th d of drug administration. White Blood Cells (WBC), Red Blood Cells (RBC), Hemoglobin (Hb), Hematocrit (HCT), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin(MCH), Mean Corpuscular Hemoglobin Concentration(MCHC), number of platelets, Differential Leucocyte Count(DLC) i.e. the percentage of neutrophils, lymphocytes, eosinophils, monocytes and basophils, neutrophil adhesion percentage, Prothrombin test (PT), Activated Partial Thromboplastin Time (APTT), fibrinogen, D-dimer, Lactate Dehydrogenase (LDH), urea, creatinine, Aspartate Amino Transferase (AST), Alanine amino Transferase (ALT), Alkaline Phosphatase (ALP), C-Reactive Protein (CRP) were evaluated and histological examination of organs were done. Results: After statistical analysis, it was found that the decrease in TLC, RBC, Hb, HCT, and LDH in Wistar rats after RNB intervention in Group A as compared to that of before RNB intervention, was found to be statistically significant (P=0.001, P=0.002, P=0.001, P=0.039, and P=0.008). On the other hand, an increase was observed in MCV, Urea, Creatinine and ALT values in the Wistar rats after RNB intervention in Group ‘A’ as compared to that of before RNB intervention and this increase in values was statistically significant (P=0.007, P=0.001, P<0.001 and P=0.038). After RNB intervention in Group B, the increase in MCH, fibrinogen concentration, and monocytes percentage, was found to be statistically significant (P=0.004, P=0.033, and P=0.001) as well as the decrease in PT and APTT was statistically significant (P=0.007and P=0.002). After comparing the Mean Hematobiochemical and coagulation test parameters in the rats of Group A and Group B, after RNB intervention, it was observed that the concentration of Urea, Creatinine, APTT, and D-dimer were less in Group B as compared to that of Group A and this difference was statistically significant(P<0.001, P<0.001, P<0.001 and P=0.022). Histologically the findings in the lungs of group B were more distortion of lung architecture, most of the alveoli become collapse and make emphysematous changes, more diffuse inflammatory infiltrate within interalveolar septa and around bronchioles as compared to Group A. In the liver of group B rats, the histological findings were mild to moderate distortion of lobular architecture, healthy hepatocytes with more activation of kupffer cells as well as larger and more aggregates of inflammatory cells as compared to group A. Histological findings of kidneys in group A and group B rats were similar to that of control group rats. Conclusion: The results suggest that the RNB is having an immunomodulatory effect. It might be helpful in the restoration of coagulation factors and can help treat the COVID patients. No harmful effects on the lungs, liver, kidney, and spleen were seen. These findings may act as baseline data for planning further clinical trials in human study subjects to evaluate the effects on various comorbidities.