IgM Multiple Myeloma Presenting With Diarrhea

Introduction: IgM Multiple Myeloma (MM) is a rare subtype of MM consisting of <1% cases of MM. It is distinguished from Waldenstrom Macroglobinemia, which also produces IgM, by the absence of somatic mutation MYD88. We present a patient with a chief complaint of diarrhea which unknowingly led to his hematological diagnosis Case Description/Methods: A 64 year old male with RA-SLE overlap syndrome on steroids, and recent COVID19 pneumonia, had presented with 5 episodes of watery diarrhea every day and 40 Ib weight loss within 2 months. CT revealed small bowel enteritis and stool studies, including C. diff, cultures, ova and parasites were negative. Diarrhea persisted despite antibiotics, therefore an EGD and Colonoscopy were performed which showed duodenal lymphangiectasia and a normal colon. Duodenal biopsy revealed eosinophilic deposits in the villous lamina propria which stained for IgM and stained negative under congo red ruling out amyloidosis. SPEP and a bone marrow biopsy revealed monoclonal IgMspikes and plasma cells in the bone marrow suggesting MMalong with a co-existing population of CLL. Next-generation sequencing was negative forMYD88, supporting IgM MM instead of Waldenstrom. He developed a protein-losing enteropathy with dramatic hypoalbuminemia (albumin 0.9) and lower extremity edema and DVTs. He was started on chemotherapy and frequent albumin infusions. His diarrhea completely resolved, however not in time, as his other medical comorbidities lagged behind and he developed anasarca and continued to deteriorate. Discussion(s): Plasma cell dyscrasias such as IgM MM or more commonly Waldenstrom have rarely been reported to cause GI symptoms. GI involvement can include direct GI infiltration of plasma cells, IgM deposition, or the finding of a plasmacytoma. It has been speculated that IgM deposits can lead to interstitial viscosity and obstructive lymphangiectasia leading to diarrhea and a protein-losing enteropathy as in our patient. Protein loss has led him to have hypoalbuminemia and possibly loss of antithrombotic proteins that have caused DVTs. Few case reports have suggested that treating the underlying cause with chemotherapy stops diarrhea entirely. Although our patient's diarrhea ceased, we believe that it was not in time for him to entirely recover from the later complications of the disease. We hope that this case can help clinicians to attempt prompt treatment of patients when they find GI specimens showing IgM deposits and they suspect a plasma cell dyscrasia.

Collapsing glomerulonephritis in a COVID-19 patient. Case report

Acute renal injury due to collapsing glomerulonephritis is associated with high morbidity and mortality, requiring chronic dialysis, COVID-19 is one of its causes. A 17-year-old male patient presented with a four-month history of edema, foamy urine and reduction in the urine flow;anasarca was observed at physical examination. Laboratory values showed creatinine 4,2 mg/dl;albumin 1,9 gr/dl;cholesterol and triglycerides were high;proteinuria 6,7 gr/24h: leucocyturia and hematuria with negative urine culture. Serologies for HIV, syphilis and hepatitis were negative. Studies for systemic lupus were negative. An antigenic test for SARS-CoV-2 was positive as well as an IgG. Renal Biopsy showed Focal and Segmental Glomerulosclerosis, Collapsing variant. He received corticosteroids and cyclosporine. Creatinine improved;proteinuria remained >3 gr/24 hours.Copyright © Universidad Peruana Cayetano Heredia, Facultad de Medicina Alberto Hurtado. All Rights Reserved.

Covid-19 Vaccination Induced Minimal Changed Disease

Introduction: Minimal change disease (MCD) accounts for approximately 15% of adults with idiopathic nephrotic syndrome (NS). We report the case of minimal change disease in a patient who presented with signs and symptoms of NS following Covid-19 immunisation vaccine. Method(s): Case: A 58-year-old male with negligible past medical history developed generalised swelling 2 days following receiving the Pfizer Covid-19 booster. On examination, he had a blood pressure of 130/80 and anasarca. Relevant laboratory results include a creatinine of 123, estimated glomerular filtration rate (eGFR) of 55, albumin of 9, urine protein: creatinine ratio of 713, and hyaline casts of moderate quantity. A kidney biopsy revealed glomerular sclerosis appropriate for age, and normal vessels and tubules. Immunofluorescence showed negative serology. A diagnosis of minimal change disease was made. The patient was treated with high dose prednisone at 1mg/kg/day and went into remission. The patient was followed up 2 months after admission, and investigations revealed a creatinine of 70, eGFR of >90, albumin of 34 and urine protein:creatine ratio of 58. Result(s): / Conclusion(s): Discussion and conclusion: This is the first case of Covid-19 vaccination induced NS reported in New Zealand. Theorised mechanism of injury includes T-cell mediated immune dysregulation, leading to glomerular disease (Sahin et al., 2020). Different glomerular diseases have been reported to occur for the first time following the Covid-19 vaccination (Klomjit et al., 2021). There has also been reports of reactivation of disease following Covid-19 immunisation (Hartley et al., 2022 and Leong et al., 2021). mRNA vaccination induced NS should be considered in all patients presenting with apparent idiopathic NS. This is especially important as we continue to learn more about the Covid-19 vaccination. No conflict of interestCopyright © 2023

An Interesting Case of Inflammatory Myositis

Background: Idiopathic inflammatory myopathies (IIM) are a class of long-lasting autoimmune diseases that typically affect the proximal muscles. Dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myopathy (NAM), and sporadic inclusion body myositis are the most prevalent kinds. Patients usually have subacute to chronic proximal weakness, which presents as difficulty getting out of a chair, getting up the stairs, lifting objects, and brushing their hair. They are distinguished by their clinical presentation, which includes muscular and ex-tramuscular signs. Elevated serum creatine kinase (CK) levels and myositis-specific antibodies may help distinguish clinical phenotypes and confirm the diagnosis. Biopsy of the muscle, on the other hand, is still the gold standard for determining the cause of the problem. These disorders may be cured with proper diagnosis and treatment. The treatment's goals are to reduce inflammation, restore muscle performance, and alleviate pain. Method(s): 36-year-old man K/C/O dermatomyositis came complaints of redness swelling in the right eye for 3 months, dysphagia, easy fatiguability. Patient was neither hypertensive nor diabetic. Result(s): This case describes the severity of NXP2 autoantibody and a potential to be life threatening. Patient was started with immunoglobulins, monoclonal antibodies. After which patient improved from his present condition.Copyright © 2022 Novyi Russkii Universitet. All rights reserved.

Adult onset refractory nxp2 dermatomyositis following covid 19 infection

Background: Dermatomyositis is a type of systemic inflammatory autoimmune disorder characterised by muscle inflammation and skin rashes. We present a rare adult onset refractory Nxp2 dermatomyositis following COVID 19 infection Methods: 36-year- old male came with the complaints of: Redness of right eye, Easy fatgiuability ,dysphagia of 3 months duration * Patient had uncomplicated COVID-19 1 month prior to onset of present complaints * On examination he had anasarca proximal muscle weakness and muscle tenderness and had neck and pharyngeal muscle weakness dysphagia and nasal regurgitation.He also had malar rash and periribital rash and swelling (Figure 1) * Investigations revealed biochemical radiological and Electrophysiological evidence of myositis (Table 1) * He was managed with pulse sterids ivig rituximab and tacrolimus with gradual but definite resolution Conclusion(s): Auto-antibodies against NXP2 are detected in 15% to 25% cases of Juvenile dermatomyositis and in only 1% of adult cases. This form of DM is characterized by accompanying calcinosis and severe and chronic disease course and is often carcinoma-associated (breast, uterine or pancreatic carcinoma). Post COVID NXP2 DM has not yet been reported. (Figure Presented).

A Case Series on Glomerular Disease Manifesting for the First Time after Covid 19 Vaccination

BACKGROUND: Different vaccines have been developed against SARS nCoV 19 and deployed in mass immunization campaigns across the world. In India, Covishield (ChAdOx1 nCoV-19) manufactured by Serum Institute of India) and Covaxin (BBV152) manufactured by Bharat Biotech are two such vaccines that have been made available. The former is a replication-deficient adenovirus vaccine while the latter is an inactivated whole virion vaccine. There has been many case reports of new onset or relapse of glomerular disease occurring after Covid-19 vaccination. This is attributed to heighten off target effect of immune response of the vaccine. AIM OF THE STUDY: We present a case series of four patients where glomerular disease manifested for the first time after Covid-19 vaccination in our center. METHOD(S): We have included in our case series those patients whose clinical features manifested for the first time within 1 month of Covid-19 vaccination and whose renal biopsy showed glomerular pathology. RESULT(S): Case 1: A 12-year-old male presented to us with abrupt onset of edema leading to anasarca on 30/4/2022. He had received first dose of Covid-19 vaccine (Covaxin) on 26/4/2022. His labs showed urine protein of 3+ and nil RBC, serum creatinine 0.7 mg/dl, serum albumin 1.9 mg/dl, and dyslipidemia (total cholesterol 378 mg/dl, triglycerides 191 mg/ dl). He underwent renal biopsy in view of nephrotic syndrome. It was suggestive of minimal change disease. He was started on prednisolone at 2 mg/kg/day. Case 2: A 39-year-old female presented to us with abrupt onset of maculopapular rash, fever, and bilateral lower limb swelling on 25/1/2022. She had received second dose of Covid-19 vaccine (Covishield) on the same day in the morning. She was found to have hypertension with BP of 160/100 mm Hg. Her labs showed urine protein of 2+ and 18-20 RBC/high power field, serum creatinine 1.9 mg/dl, serum albumin 3.7 mg/dl, negative ANA and ANCA, and normal complement levels. She underwent renal biopsy in view of renal failure with active urinary sediments. It was suggestive of focal and segmental glomerulosclerosis (FSGS). Case 3: A 37-year-old male patient with history of hypertension (on irregular treatment) presented to us with history of gross hematuria without passage of clots in May 2022 about three days after receiving booster dose of Covishield vaccine. He did not have edema, rash, joint pain, or decreased urine output. His labs showed urine protein of 2+ and 5-6 RBC/high power field, serum creatinine 2.0 mg/dl, serum albumin 4.0 mg/dl, negative ANA and ANCA, and normal complement levels. He underwent renal biopsy in view of renal failure with active urinary sediments. It was suggestive of IgA nephropathy (M1E0S1T1C0). Case 4: An 18-year-old female with family history of nail patella syndrome presented to us with history of abrupt onset of edema of both lower limbs on 21/11/2021. She also had rash at the time of presentation. She had received first dose of Covid-19 vaccine (Covaxin) on 20/11/2021. Her labs showed urine protein of 2+ and numerous RBC/high power field, serum creatinine 1.4 mg/dl, serum albumin 2.98 mg/dl, negative ANA, and dsDNA and low complement levels (C3 14.1 mg/dl, C4 10.1 mg/dl: both being low). She underwent renal biopsy in view of renal failure with active urinary sediments. It was suggestive of membranoproliferative glomerulonephritis (MPGN). She was started on prednisolone at 1 mg/kg/day. CONCLUSION(S): Different vaccines have different mechanisms of action, but their target remains the spike protein of the SARS Cov2 virus. Glomerular disease has mostly been reported with mRNA-based vaccines. Here we have reported glomerular disease occurring in close temporal relation to Covishield and Covaxin which have different mechanism of action. There have been reports of IgA nephropathy, minimal change disease and FSGS which manifested soon after vaccination. MPGN after Covid-19 vaccination is rarely seen. Thus, this case series shows that post- Covid vaccination glomerular disease can have varied pathologies.

A rare case of intravascular diffuse large B-cell lymphoma with secondary hemophagocytic lymphohistiocytosis

Introduction Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and potential life-threatening syndrome characterized by excessive immune activation and cytokine release. In adults, infections, inflammatory diseases and more rarely hematological malignancies can trigger the onset of HLH. We describe a rare case of intravascular diffuse large B cell lymphoma (DLBCL) associated with HLH. Case presentation A 53-year-old woman, presenting with high fever since 3 weeks and asthenia, was admitted to the hospital. She had a negative medical and travel history. On physical examination, generalized edema and hypotension were noted. An extensive bacterial and viral work-up (including COVID-19) was negative. During admission, the patient developed progressive anasarca and an episode of epileptic convulsions. Laboratory results showed increasing cytopenia, major hyperferritinemia, hypofibrinogenemia and hypertriglyceridemia. A bone marrow examination showed prominent hemophagocytosis. Cerebrospinal fluid examination showed the presence of aberrant monocytes, indicating CNS involvement. Genetic analysis to detect hemophagocytosis-associated mutations was negative. PET-CT revealed increased FDG uptake in both adrenal glands, hypophysis, bone marrow and spleen. Biopsy of the adrenal gland was not contributive. Brain MRI showed two cerebral masses radiologically suggestive for meningioma, confirmed by histology. The patient was refractory to high-dose corticotherapy and treatment was adapted to the HLH-94 protocol. A blind skin biopsy showed the presence of a population of pathological B-lymphocytes with aberrant immunophenotype (CD20+/Pax5+/Bcl6+/Bcl2+/cMYC-) in and around the small blood vessels leading to the diagnosis of intravascular DLBCL. Treatment was adjusted to lymphoma-specific immune-chemotherapy upon which a gradual clinical improvement was noted. After four cycles R-CHOP, three cycles of high dose methotrexate and high dose Endoxan for stem cell mobilisation, treatment was intensified with two cycles R-DHAP because of laboratory signs of persistent hemophagocytosis. Thereafter, the patient received an autologous stem cell transplantation (auto-HCT) after BEAM chemotherapy. End of treatment PET-CT and skin biopsy documented complete remission of the lymphoma. Because of slow hematological recovery, repeated bone marrow examinations were done and showed hypoplasia and persistent hemophagocytosis. Dexamethasone in combination with eltrombopag led to a gradual hematological response. At 20 months after auto-HCT, the patients stay in complete remission of the DLBCL and are independent of corticotherapy, with acceptable hematological parameters and no clinical signs of HLH. Discussion In the absence of infection, HLH is a diagnostic challenge frequently leading to delayed identification of the primary trigger, if any. A characteristic image on PET-CT with increased uptake in adrenal glands and hypophysisis led us to perform a blind skin biopsy to diagnose intravascular DLBCL, a rare subtype of lymphoma. Our case also shows that 1) HLH is very difficult to manage without dealing with the primary trigger and 2) HLH can persist for prolonged periods of time after successful treatment of the primary cause and may require specific therapy for sufficient control.

Differences in Mortality Rates in Inpatients with Cirrhosis Depends on the Low, Middle or High Income Country Location: Multi-National Cleared Consortium Experience

Background: Although cirrhosis is a major cause of mortality worldwide, there could be disparities in outcomes. This needs a global consortium to study disparities in inpatient cirrhosis care Aim: Define the impact of location in prediction of outcomes in inpts with cirrhosis. Method(s): CLEARED prospectively enrolled non-electively admitted cirrhosis pts without COVID from all continents. To ensure equity, we allowed only 50 pts/site. Admission details, cirrhosis history, inpatient & 30-day course were recorded. World bank classification of low/low middle income (LMI), upper middle (UMI) & High income (HI) were used. Cirrhosis details, inpatient & 30-day outcomes were compared between groups. Multi-variable regression was performed using inpatient & 30-day mortality as outcomes. Result(s): 2758 pts from 21 countries from all continents, including Africa & Australia, were included.727 were L/LMI, 1050 UMI & 981 pts were from HICs. More men & younger pts were in LMI. Cirrhosis details: More pts in HI gp had 6M hospitalizations & infections, HE & ascites while prior variceal bleeding was higher in LMI . Prior HCC & transplant listings were lower in LMI but similar in UMI/HI. Alcohol & NASH was highest in HI. Viral hepatitis & cryptogenic were highest in UMI.Admissions: Admission MELD was highest in LMI. LMI pts were admitted more for GI Bleed, HE, & DILI, while anasarca & HBV flares were higher in UMI. Higher SBP (36% vs 24% vs 21% p<0.0001) & lowest skin/soft-tissue infections were in LMI (5% vs 5% vs 10% p=0.008);rest were similar. Nosocomial infections, driven by UTI were highest in LMI & HI pts (15% vs 14% vs 11% UMI, p=0.03). Admission diuretics, PPIs, Lactulose & statins were highest & antivirals lower in HI. SBP prophylaxis & rifaximin were highest in LMI pts. Outcome(s): More LMI pts needed ICU & had more organ failures (Fig B). Discharge MELD was highest in LMI. In-hospital mortality was highest & transplant lowest in LMI. This extended to 30-day mortality & transplant in LMI patients vs HI pts.Regression: In-hospital mortality was linked with age, infections, MELD & being in a LMI/UMI vs HIC while being on a transplant list, diabetes, & SBP prophylaxis were protective (Fig C). 30-day mortality predicted by age, ascites, HCC, discharge MELD, organ failures, LMI/UMI vs HIC but rifaximin was protective(Fig D). In-hospital transplant was higher with high MELD, admission rifaximin & listed pts &lower in LMI (OR 0.26) & UMI (OR 0.22) & age. 30-day transplant was higher in those with hyponatremia, ascites & HRS, on the list & on rifaximin and lower in LMI (OR 0.24) & UMI (OR 0.59) vs HI. Conclusion(s): In a global study of inpatients with cirrhosis, there were major differences in outcomes. Not being in a high-income country significantly increased the risk of inpatient and 30-day mortality independent of demographics, medications, in-hospital course, and cirrhosis severity likely due to disparities in access to transplant, which should be accounted for in global models. (Figure Presented).

Occurrence Of Nephrotic Syndrome In A Child Post Covid

Background: The incidence of COVID infection is low in children when compared in adults, and predominantly causes respiratory symptoms yet unusual cases have been reported. Case: Presenting a girl, 6 years of age with features of nephrotic syndrome about a month after contracting a mild upper respiratory tract illness, tested positive for COVID-19 IgG antibodies, with no antecedent kidney disease. Conclusion(s): The child who presented with clinical features of Nephrotic syndrome had Anti-IgG antibodies for Sars Cov2 infection. Some articles have shown proven association with the occurrence of nephrotic/ nephritic syndrome in adults either during or post Covid 19 infection. There have been similar cases of first episode Nephrotic syndrome reported post COVID infection in children. But the numbers have not been large enough to establish any association. Whether this is just a coincidence or an established sequel of COVID-19 infection is still unknown. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Glomerular Diseases: Podocytopathies and Nephrotic Syndromes Relapsed Membranous Nephropathy After COVID-19 Vaccination

Introduction: De novo and relapsed glomerulonephritis (GN), including membranous nephropathy (MN), have been reported after COVID-19 mRNA-vaccination. We report a case of MN that relapsed following COVID-19 vaccination after 26 years of remission. Case Description: A 78-year-old man presented with nephrotic syndrome (UPC 8.0). His history was notable for primary MN diagnosed by kidney biopsy in 1994. He was treated with prednisone and ACE inhibitor with full resolution of proteinuria. He received COVID-19 vaccine (mRNA-1273, Moderna) March 3 and April 1, 2021. Between the two doses, he had onset of leg swelling. This was attributed to amlodipine, which was discontinued by his PCP. After the second dose of vaccine, edema progressed to anasarca. Urine protein was 5.73g/day. Two months later, the UPC was 8.0, serum creatinine 0.86 mg/dL, and serum albumin 2.7mg/dL. Anti-PLA2R was positive (24RU/mL, ref. >19RU/mL). Renal biopsy showed recurrent MN, EM stage 3-4, PLA2R1 positive. Due to regional surge of COVID-19 Omicron variant, immunosuppression was held to administer EvuSheld for COVID-19 prophylaxis. Proteinuria improved initially without intervention (UPC 2.7) but increased again (UPC 4.7) a month later. Rituximab was initiated three months after biopsy resulting in undetectable anti-PLA2R 1 week after treatment, with reduction in UPC to 3.7 and improvement of anasarca 2 weeks after treatment. Discussion(s): Onset or relapse of GN after vaccination historically has rarely been reported. There are numerous reports of de novo or relapsed GN after COVID-19 infection, and increasing reports of GN after COVID-19 vaccination with mRNA and traditional vaccine platforms. The pathogenesis of GN in this setting has not been established. Nonspecific immune activation and specific COVID-19-related immune reaction have been postulated. MN related to COVID-19 vaccination, although rarely reported, has been treated with standard immunosuppression with favorable results. Management of MN and other forms of GN will evolve with greater understanding of disease course in the setting of COVID-19 infection and vaccination. Patients with a history of GN, including MN, should be counseled about the possibility of relapse with COVID-19 infection or vaccination, even if their original disease was remote.

Mixed Nephrotic/Nephritic Syndrome in a Pediatric Patient With SARS-CoV-2 Infection

Introduction: Glomerular diseases in children generally present as a variety of findings that include hematuria, proteinuria, edema, and hypertension. Glomerular diseases can be isolated to the kidney or present as a component of a systemic disorder. Emerging reports show that SARS-CoV-2 infection precedes the appearance of various autoimmune diseases. Case Description: Twelve-year-old Hispanic female with history of migraines, obesity, hypercholesterolemia, and NAFLD, who presented with anasarca, fever, and fatigue. On exam, she had hypertension (138/89 mmHg) and anasarca with ascites. Labwork was remarkable for K+ 5.6 mmol/L, Cr 1.07 mg/dL, albumin 2.1 gm/dL, AST 48 IU/L, cholesterol 265 mg/dL, triglycerides 178 mg/dL, CRP 2.6 mg/dL and ESR 80 mm/hr. UA with >500 proteinuria, moderate blood, 100 RBCs, 49 WBCs, and negative leukocyte esterase and nitrites. A rapid strep test and Hepatitis Panel were negative. ANA <1:10, C3 complement level low at 36 mg/dL, C4 normal. Abdominal US showed hepatomegaly, echogenic bilateral kidneys, and a small pleural effusion. SARS-CoV2 antigen test was positive. She was managed with antihypertensives, albumin infusions, and furosemide. She was readmitted 2 weeks later from the Nephrology clinic since her creatinine was 1.5 mg/dL and she persisted with generalized edema. Repeat SARS-CoV2 PCR was negative. At this time, she presented ANA titer in >=1:1280, strongly positive SSA, SSB, and SM antibodies, low C3 (43.0 mg/dL) and low C4 (7.4 mg/dL). Renal biopsy specimens showed more than 50 percent of glomeruli affected with mesangial and extracapillary hypercellularity, segmental cellular crescents, interstitial fibrosis, and marked deposition of immunoglobulins and complement, consistent with lupus nephritis Grade IV. Discussion(s): Systemic Lupus Erythematosus (SLE) is an autoimmune condition that has been described in correlation with SARS-CoV-2 infection in adult patients. Our patient fulfills SLICC criteria for SLE and a temporal relationship exists between SARS-CoV-2 infection and the development of SLE antibodies. SARS-CoV2 has also been reported to directly cause nephritis, although with more tubular than glomerular involvement. A renal biopsy is required for accurate diagnosis.

Messenger RNA COVID-19 Vaccine-Associated Collapsing Focal and Segmental Glomerulosclerosis

Introduction: A novel coronavirus (SARS-CoV-2) mRNA vaccine was invented as a mitigation strategy to control COVID- 19 pandemic and as a promising approach to reduce the spread of COVID- 19 infection among population worldwide with impressive reduction in new COVID- 19 infection cases. We report a first case of collapsing focal and segmental glomerulosclerosis (FSGS) was diagnosed post-second dose of SARS- CoV-2 Moderna vaccine. Case Description: A 75-year-old Caucasian female with unremarkable medical history who was admitted anasarca started 6 weeks after receiving the second dose of SARS- CoV-2 Moderna vaccine. She was found to have anuric acute kidney injury, blood pressure 210/110 mmHg. Laboratory results showed serum creatinine 8.2 mg/dl, serum albumin 2.6 g/dl. Urine microscopic showed numerous granular casts and tubular epithelial cells. 24 hr. urinary collection revealed proteinuria of 6.9 g. Transthoracic echocardiogram was normal. Kidneys were normal in size with increased cortical echogenicity on renal ultrasound. Unremarkable comprehensive workup. Kidney biopsy showed segmental sclerosis with associated hyperplastic visceral epithelial cells with intracytoplasmic protein reabsorption droplets. The associated capillary loops appeared collapsed. Immunofluorescence showed segmental glomerular staining for IgM, C3 and C1q (3+). Discussion(s): Several case reports have been published suggesting a temporal association between glomerular disease and relapsing glomerular disease after receiving SARS-CoV-2 RNA (mRNA) vaccines of either Pfizer- Bio-Tech or Moderna mRNA- 1273, SARS-CoV-2 mRNA vaccines generate humoral and cell- mediated immune response by CD4 and CD8 expansion to T helper-based response with production of interferon-gamma, tumor necrosis factor- alpha, interleukin-2 and antibody production predominantly of immunoglobulin G1 and IgG subclass. That suggests cell- mediated immune reaction that may cause podocyte injury or recurrence of glomerular disease. Potential mechanism of podocyte injury post SARS- CoV-2 mRNA vaccine may be triggered by cytokine-medicated response, direct toxic effect or a rapid T cell- medicated immune response and lead to podocytopathy. Further investigations are needed to establish the causal relationship between SARS-CoV-2 and glomerular injury in susceptible individuals. Increase awareness in that regard might help to expand database of those cases.

The Mosaic of Autoimmunity

Introduction: Lupus nephritis (LN) is one of the most common manifestations affecting 45% of patients with systemic lupus erythematosus (SLE). Here we present a case of rapid progression of LN in the setting of recent COVID-19 infection, suggesting a possible synergistic cascade of cytokines contributing to rapid disease flare up. Case Description: 52-year-old hispanic lady with past medical history of hypertension and newly diagnosed SLE presented to the clinic with chief complaint of generalized anasarca, fatigue and low back ache. She was found to have a hemoglobin of 8.8 along with severe leukopenia. Urinalysis was positive for large amount of blood, protein with a protein: creatinine ratio of 9 gm. ANA titer was positive along with low levels of C3 complement and normal levels of C4 complement. Creatinine of 2.3 which was 4 times higher than her baseline. Labs from 2 months ago showed creatinine of 0.57. Of note, the patient was diagnosed with COVID-19 a month ago. She had a renal biopsy and was diagnosed with stage IV LN and was started on dialysis. Discussion(s): LN usually has an indolent course with people developing ESRD within 5 years of diagnosis of lupus. This case strikes out as a rapid progression of LN with progression to ESRD within less than 3 months of diagnosis of SLE. COVID-19 a few months before she was diagnosed with Lupus is a possible source of a cytokine storm. Suggested mechanisms of induction of autoimmunity include both molecular mimicry as well as bystander activation whereby the infection may lead to activation of antigen presenting cells that may in turn activate pre-primed auto-reactive T-cells, thus leading to pro-inflammatory mediators, which in turn may lead to tissue damage. Strategies to prevent rapid progression to ESRD in these patients needs to be studied and better understood. Perhaps patients with autoimmune conditions like SLE need more robust management of diseases like COVID-19 which is known to alter and activate the immunological cascade. As per recent literature exaggerated extrafollicular B cell response characteristic of active SLE also characterizes the B cell response to COVID-19. Understanding and targeting the B cell pathway could potentially help dampen a severe response and disease progression. Overlap including racial preponderance of disease severity also needs to be studied further.

Can PLA2R Antigen in Kidney Tissue Turn Positive After Recent COVID-19 Infection in Membranous Nephropathy?

Introduction: COVID-19 infection has been associated with variety of kidney diseases including glomerulopathies. To our knowledge, only 8 cases of membranous nephropathy post COVID infection have been reported so far out of which 3 were PLA2R antigen positive. We report another case of such a rare association. Case Description: 33 y/o AA obese male admitted with worsening anasarca for 1 month. His labs showed normal kidney function, hypoalbuminemia and nephrotic range proteinuria of 4 g/d. Urinalysis was otherwise bland. Serology including ANA, ANCA, C3, C4, Anti-PLA2R, Hepatitis panel, HIV were all negative. USG showed normal kidneys. Kidney biopsy was done which showed membranous nephropathy. There were no signs of virus in the kidney tissue. He stained positive for PLA2R antigen. Further history revealed that he had mild COVID infection 2 weeks before the swelling started. He did not require hospital admission. For his kidney disease, he is started on losartan and diuretics. He is being observed for 6 months for possible spontaneous resolution. Discussion(s): Based on the clinical presentation and serology it would suggest that the patients with COVID-19 infection may be associated with subsequent membranous nephropathy. The clinical presentation of the infection two weeks prior may be the stimuli for the PLAR2 antigen and the membranous nephropathy, while the serum anti-PLA2R antibody was negative.

Severe progression of autoimmune hepatitis in a young COVID-19 adult patient: A case report

Rationale: The impact of COVID-19 in patients with autoimmune liver disease treated with immunosuppressive therapy has not been described so far. This case report describes the clinical course of a patient with autoimmune hepatitis (AIH) who developed COVID-19 and the features of cytokine syndrome leading to its deterioration in our intensive care unit. Patient's Concern: A 28-year-old male presented with generalized anasarca for two weeks and chronic liver disease for 8 months. Diagnosis: AIH and Covid-19 with features of cytokine storm syndrome. Interventions: Intravenous furosemide, mannitol, syrup lactulose, steroids (prednisolone 40 mg), azathioprine 1 mg/kg body weight, rifaximin, vitamin K, and blood products. Outcomes: The patient had hepatic encephalopathy and AIH and died on the 10th day after admission despite ventilatory support, sustained low-efficiency hemodialysis, and resuscition. Lessons: The dramatic release of cytokines and the inflammatory-immune responses not only alter the pathophysiology but also affects the onset and severity of disease progression in patients with AIH.

OVARIAN CARCINOMA MIMICKING SYSTEMIC SMALL VESSEL VASCULITIS: CASE REPORT

Background: Few cases of digital ischemia and gangrene associated with primary solid tumors have been described in literature[3]. The exact mechanism of severe occurrence has not been completely understood and the available treatment options have an extremely limited utility [1,2].In the most cases the patients were elderly women with adenocarcinomas of digestive or gynaecologic apparatuses [4]. Objectives: We describe a new case of digital gangrene as unusual presentation of ovarian cancer in a 36 years old woman. Methods: 36 years old female was admitted to our Reheumatology deparment with blackish Blackish discoloration of the toes of one week duration. She had history of COVID-19 infection 8 months prior to the presentation then developed hemoptysis, picture suggestive of ILD, generalized anasarca and skin rash;accordingly an initial diagnosis of post COVID-19 vasculitis was made by dermatologist. The blood tests were ESR:21 mm/hr, CRP:25.7, D.Dimer:8.8, Ferri-tin:575 ng/ml, lymphopenia:0.9, S.Creatinine:2, 24 h urinary protein: 325 mg/24h and all autoimmune markers were negative except anti nuclear antibody (ANA) with titer:1/160. Further assessment revealed that she had multiple site coag-ulopathy;internal jugular vein thrombosis, bilateral lower limbs Deep Venous Thrombosis (DVT). Neck ultrasound surprisingly showed bilateral enlarged suspicious looking supraclavicular lymph node with lost hilum which was Biopsied for histopathological correlation which revealed focally necrotizing adenocarci-noma with signifcant signet ring differentiation. Searching for the primary malignancy, tumor markers were sent CA125: 584 u/ml (up to 35), Pelvi-abdominal Magnetic resonance imaging (MRI) revealed Left ovarian mass measuring 3.6 x 3.4 x 4.4 cm highly suspicious of malignant neoplastic growth for histopatho-logical correlation, Suspicious looking pelviabdominal lymph nodes mostly representing malignant lymphadenopathy, Scattered peritoneal nodules suspicious of metastatic deposits. Results: During admision the patient received full dose anticoagulation (Low Molecular Weight Heparin: 60 iu/12 h). Upon diagnosis we arrange the transferal to the oncology department to continue her management plan. Unfortunately;the case was terminal for palliative therapy and she died after 2 weeks. Conclusion: Bluish discoloration of digits and toes may be a clue for diagnosis of many diseases not only vasculitis. Malignancy can disturb the immune system in a way that mimic any systemic connective tissue disease. Acute insult aggressive multiple site deep venous thrombosis (DVT) necessitate thinking outside the box and consider other causes of coagulopathy like visceral malignancy.

Neonatal Acute Liver Failure in a Preterm Neonate with Gestational Alloimmune Liver Disease and Congenital Portosystemic Shunts

Introduction: Gestational alloimmune liver disease (GALD) is a leading cause of neonatal acute liver failure (NALF), a rare but important diagnosis. Congenital portosystemic shunts (CPSs) are rare vascular anomalies that leave patients at risk for developing a wide spectrum of complications and have not been previously associated with GALD. In this case, we present a newborn male with NALF secondary to GALD complicated by intrahepatic shunts. Case Description: The patient is a 30 weeks gestational age male born to a 28-year-old gravida 2 para 0 mother via urgent cesarean section for severe placental malperfusion. The pregnancy was complicated by severe intrauterine growth restriction, oligohydramnios, and maternal COVID-19 infection. The patient's initial NICU course was remarkable for respiratory distress requiring ventilatory support, hypotension requiring inotropes and stress dose steroids, and coagulopathy with bleeding requiring transfusion of multiple blood products. An abdominal ultrasound showed large congenital intrahepatic portosystemic shunts. Over the course of the hospitalization, the infant progressed to fulminant hepatic failure with associated coagulopathy, hypoalbuminemia, direct hyperbilirubinemia, and hyperammonemia. There was persistent anasarca in addition to elevated ferritin (1,922 ng/dL) and alpha-fetoprotein (97,855 ng/mL). Serial SARS-CoV-2 NAAT were negative. In consultation with the hepatologist there was high clinical suspicion for GALD, and treatment with intravenous immunoglobulin was initiated, however, no clinical or laboratory improvement was noted. Abdominal MRI showed progression of the large CPSs and enlargement of the hepatic arteries. The infant continued to deteriorate, was transitioned to comfort care, and died on day of life 82. A limited autopsy revealed a markedly edematous and jaundiced male with grossly enlarged liver with hepatocellular cholestasis, portal fibrosis, diffuse hepatobiliary iron depositions, and C5b9 positivity within hepatocytes confirming a diagnosis of GALD. Discussion: Neonatal hemochromatosis is the phenotypic result of severe liver injury leading to iron overload and extrahepatic siderosis, the mechanism of hepatic injury now recognized in GALD. Liver failure in newborns with GALD often presents with marked coagulopathy, hypoalbuminemia, and edema with and without ascites. The establishment of the diagnosis is crucial given without treatment, the prognosis is very poor. There have been no case reports of neonates with acute liver failure from CPSs or CPSs occurring with GALD. We hypothesize that the presence of CPSs worsens the clinical course of GALD through an unknown mechanism that further expedites hepatocellular damage. Furthermore, the role of SARS-CoV-2 infection and transmission in the neonatal population is still unknown. Conclusion: Neonatal acute liver failure caused by GALD is a rare but potentially fatal diagnosis. CPSs associated with GALD have not been previously documented. This case demonstrates the interplay of these disease entities likely contributing towards a more severe course of NALF and highlights the importance of early identification for guiding management. (Figure Presented).

CLEARED Global consortium results highlight regional variation and need for equity in inpatient outcomes in hospitalized patients with Chronic Liver Disease

Background and aims: A global study with equitable participation for cirrhosis and chronic liver disease (CLD) outcomes is needed. We initiated the Chronic Liver disease Evolution And Registry for Events and Decompensation (CLEARED) study to provide this global perspective. Aim to evaluate determinants of inpatient mortality and organ dysfunction in a multi-center worldwide study. Method: We prospectively enrolled pts with CLD/Cirrhosis >18 years without organ transplant or COVID-19 who were admitted non-electively. To maintain equity in outcome analysis, a maximum of 50 pts/site were allowed. Data for admission variables, hospital course, and inpatient outcomes (ICU, death, organ dysfunction [ODF]) were recorded. This was analyzed for death and ODs using significant variables on admission and including World Bank classification of low/middle-income countries (LMIC). A model for in-hospital mortality for all variables during the hospital course, including ODs) was analyzed. Results: 1383 pts (55 ± 13 yrs, 64% men, 39% White, 30% Asian, 10% Hispanic, 9% Black, 12% other) were enrolled from 49 centers (Fig A). 39% were from high-income while the rest were from LMICs. Admission MELDNa 23 (6–40) with history in past 6 months of hospitalizations 51%, infections 25%, HE 32%, AKI 23%, prior LVP 15%, hydrothorax 8% and HCC 4%. Leading etiologies were Alcohol 46% then NASH 23%, HCV 11% and HBV 13%. Most were on lactulose 52%, diuretics 53%, PPI 49% and statins 11%, SBP prophylaxis 16%, beta-blockers 35% and rifaximin 31%. 90% were admitted for liver-related reasons;GI bleed 30%, HE 34%, AKI 33%, electrolyte issues 30%, anasarca 24% and 25% admission infections. In-hospital course: Median LOS was 7 (1–140) days with 25% needing ICU. 15% died in hospital, 3% were transplanted, 46% developed AKI,15% grade 3–4 HE, 14% shock, 13% nosocomial infections and 13% needed ventilation. Logistic Regression: Fig B shows that liver-related/unrelated factors on admission which predicted in-hospital mortality and development of organ dysfunction with MELDNa and Infections being common among all models. Nosocomial infections and organ dysfunctions predicted mortality when all variables were considered. High-income countries had better mortality outcomes likely due to transplant and ICU availability. AUCs were >0.75 (Figure Presented) Conclusion: In this worldwide equitable experience, admission cirrhosis severity and infections are associated with inpatient outcomes, which are greater in low-income settings. Liver-related and unrelated factors and regional variations are important in defining critical care goals and outcome models in inpatients with cirrhosis.

Undifferentiated Shock: A Case of Idiopathic Capillary Leak Syndrome

Systemic capillary leak syndrome (SCLS or Clarkson's disease) is a rare condition characterized by episodes of vascular hyperpermeability. The extravasation of plasma to the interstitial space results in hemoconcentration, hypoalbuminemia, hypovolemia and compartment syndrome of the extremities. The disease can be idiopathic or secondary to causes including viral infections or chemotherapeutic toxicity. We present a fatal case of idiopathic SCLS which rapidly deteriorated to multiple organ failure despite initial improvement with methylene blue. A 57-year-old male presented for worsening back pain over one month. He described a flulike illness 2 weeks prior. Testing for respiratory viruses including SARS-CoV-2 was negative. He received intravenous crystalloid fluids acutely developed respiratory distress and hypotension requiring emergent intubation and initiation of norepinephrine infusion. CT angiography of the chest demonstrated pulmonary edema. Early during his hospitalization urine output ceased and body weight increased by 10 kg, developing tense anasarca. Hematocrit concentrated from 42.7 to 54.4%. Serum albumin dropped from 4.6 to 2.5 g/dL. C1 esterase inhibitor level and IgM were normal. Ferritin was elevated at 2515 ng/ml. He received cefepime and vancomycin, though infectious workup returned unremarkable. Continuous renal replacement therapy and stress dose steroids were initiated. Vasopressor requirement worsened until he was on three vasopressors at one point. Given the constellation of hemoconcentration, hypoalbuminemia, and shock a diagnosis was made of idiopathic SCLS. Treatment was started with methylene blue, montelukast, and the β-adrenergic agonist terbutaline. Blood pressure improved and patient came off pressors and lactate improved from 13 to 4. However, he later developed rising creatine kinase continued to climb to >40,000 U/L. He developed rhabdomyolysis with concern for compartment syndrome of the extremities due to third spacing of fluids. Orthopedic surgery was consulted;but did not believe a fasciotomy was indicated due to rapid decline. Lactic acidosis rose to 18 mmol/L. His family decided to transition to comfort measures. He passed with family at bedside on Day 4 of hospitalization. There are fewer than 500 cases of SCLS reported since initial discovery in 1960. Given the overlap in presentation with common causes of plasma leakage such as sepsis, it is likely that many cases are unrecognized. Patients are often mismanaged;development of severe hypovolemia despite fluids and compartment syndrome is overlooked. This case builds on our evolving recognition of this disease, and the potential for the use of methylene blue to help acute exacerbations of the disease.

DE NOVO DOUBLE GLOMERULOPATHY (MEMBRANOUS NEPHROPATHY, MN AND COLLAPSING FOCAL SEGMENTAL GLOMERULOSCLEROSIS, CFSGS) ASSOCIATED TO POSITIVE MYELOPEROXIDASE-O (MPO) ANTIBODY FOLLOWING PFIZER - BIONTECH MRNA VACCINATION COVID 19

BACKGROUND AND AIMS: In the COVID 19 pandemic era, anti SARS-CoV-2 vaccination showed high efficacy at preventing the infection and its most severe complications. The aim of this report is to describe an unusual double glomerulopathy related to anti SARS-CoV-2 vaccination and the good results obtained with the immunosoppressive treatment. METHOD: An 80-year-old caucasian woman developed a nephrotic syndrome, progressive renal insufficiency and microhematuria. The patient presented a medical history of thrombocytopenic purpura treated and resolved by steroids in 2013, hypothyroidism, hypertension, ischaemic heart disease treated with surgical bypass in 2019 and pacemaker in 2020 for atrial ventricular block. Due to pandemic COVID 19 status, she received two doses of the Pfizer BioNTech mRNA COVID-19 vaccine in March 2021. Two weeks after the second dose her weight increased of 23 kg. The family physician added furosemide to her therapy for generalized edema with no diuretic effect. In April, creatinine was 1.38 mg/dL (versus 0.8 mg/dL 1 year before);urinalysis showed proteinuria (300 mg/dL) and microscopic hematuria;serum total cholesterol level was 218 mg/dL and triglycerides 178 mg/dL;then it was suggested to increase the doses of furosemide. In May 2021, creatinine resulted 2 mg/dL, serum albumin 2 g/dL, and urinalysis confirmed proteinuria and microscopic hematuria;proteinuria was 10 g/day. Abdomen ultrasound showed normal liver, kidneys and spleen, not ascites. Lower limb eco-Doppler showed right superficial femoral artery stenosis of 60% and absence of venous thrombosis. The physical examination evidenced anasarca. The patients were admitted to the nephrology unit;hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus antigen and antibody were negative. Both complement C3 and C4 levels resulted within the normal range. Cryoglobulins were absent. Urinary Bence Jones, antinuclear antibody (ANA), anti-extractable nuclear antigen (ENA), anti-double stranded DNA (nDNA) antibodies were negative. Antineutrophil cytoplasm antibodies (ANCA) were 1:2560 with Perinuclear pattern and anti-MPO positivity (716 UA/mL);anti-proteinase-3 antibodies (PR3) were negative. Antiphosholipase A2 receptor antibody (PLA2R Ab) was positive with high titre. A kidney biopsy was performed showing a double nephropathy: a focal segmental glomerulosclerosis (FSGS) with some collapsing features, superimposed on membranous glomerulonephritis (Fig. 1). RESULTS: We started the Ponticelli regimen (alternate months steroids and cyclophosphamide). After the first month of therapy, blood tests revealed creatinine 1.7 mg/dL, haemoglobin 11.7 g/dL;serum albumin 2.7 g/dL and urinalysis without microscopic haematuria. At the third month of therapy, the patient developed atrial fibrillation and started anticoagulation;blood tests were as follows: creatinine 1.1 mg/dL, serum albumin 3.0 g/dL, Ab anti-MPO 7 UA/mL and PLA2R Ab was absent. A left ocular, frontal and parietal herpes zoster induced a short discontinuation of therapy and responded well to Acyclovir;then we concluded the fourth month of therapy. At the fifth month, a SARS CoV 2 RT PCR unexpectedly resulted positive;the patient remained asymptomatic, but we stopped definitively the therapy. One month later, blood tests showed: creatinine 1 mg/dL, serum albumin 4 g/dL, proteinuria 0.7 g/die, MPO 2 UA/mL and PLA2R Ab absent. CONCLUSION: To our knowledge, this is the first case of nephrotic sindrome secondary to a De novo MN and FSGS, associated with positive MPO antibody, following Pfizer-BioNTech mRNA vaccination COVID 19;the patient responded well to immunosoppression going in remission and regaining renal function. (Figure Presented).