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Introduction: Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS), is a clinical syndrome characterized by hepatomegaly, right-upper quadrant pain, and ascites that occurs most commonly in the setting of high-dose chemotherapy or hematopoietic stem cell transplantation (HSCT). The diagnosis can be confirmed on biopsy. Cemiplimab is an immune checkpoint inhibitor recently approved for the treatment of cutaneous squamous cell carcinoma. There are currently no known reports of immune checkpoint inhibitor-related VOD/SOS. Case Description/Methods: A 58-year-old female with a history of locally advanced basal cell carcinoma of the left eye treated with six months of Cemipilimab presented with ascites. On admission, labs were notable for a total bilirubin of 1.2, mildly elevated liver function tests, alkaline phosphatase 884, and international normalized ratio 2.1. A diagnostic tap revealed a high SAAG ascites that was negative for infection. A comprehensive serological workup for viral, metabolic and autoimmune causes was unrevealing. A transjugular liver biopsy demonstrated a hepatic venous pressure gradient of 18mmHg, nodular regenerative hyperplasia (NRH), and portal venopathy. The patient was discharged on steroids but returned one month later for recurrent ascites and worsening bilirubin to 12.6 (direct 7.3);COVID PCR was negative. A full rheumatologic and vasculitis workup was unremarkable. Repeat biopsy (Figure 1) demonstrated moderate NRH changes, prominent central vein sclerosis with fibrous obliteration, signs of SOS/ VOD and central venulitis with fibrotic changes with sinusoidal portal hypertension. Discussion(s): VOD occurs most often with hematopoietic stem cell transplantation, and chemotherapeutic agents. Here we present the first case of checkpoint inhibitor-induced VOD/SOS. Despite discontinuation of the offending agent and a trial of steroids, the patient's clinical course continued to deteriorate. She eventually developed refractory ascites and portosystemic encephalopathy. She was deemed not a candidate for liver transplant given her underlying malignancy. She was transitioned to home hospice before further treatment, such as Defibrotide could have been pursued. VOD associated with immune checkpoint inhibition should be considered in the differential of patients who develop new onset liver dysfunction and ascites while receiving these medications (Figure Presented).
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Introduction: Primary membranous nephropathy (MN) is most commonly due to phospholipase A2 receptor antibodies (PLA2R Ab). It is unclear whether the COVID-19 vaccine can trigger flares of glomerular diseases such as primary MN. We present a patient with MN and metastatic breast cancer who developed nephrotic syndrome after receiving her second mRNA-1273 COVID-19 vaccine with positive PLA2R Ab by ELISA suggesting MN flare. Case Description: A 62 year old female with history of Stage IIIB T3N3M1 ER/PR positive HER-2 negative metastatic left breast invasive ductal carcinoma, hypertension, hyperlipidemia, and primary MN presented with bilateral leg edema, dyspnea, and proteinuria 2 weeks after COVID-19 vaccination. She had previous proteinuria of 7029 mg/24hr in August 2018 with PLA2R Ab 128 RU/mL in October 2018. She underwent modified radical mastectomy in September 2018 followed by adjuvant chemotherapy in November 2018, after which PLA2R Ab decreased to <2 RU/mL in February 2019 and urine protein/Cr ratio (UPCR) decreased to 1094 mg/g Cr in April 2019. She was diagnosed with metastatic breast cancer and started anastrazole transiently. She received mRNA-1273 COVID-19 vaccines in late January and February 2021. In March 2021, she presented with bilateral leg edema, dyspnea, and bilateral pleural effusions. Urinalysis had >1000 protein, 24hr urine protein 11.2 g, Cr 1.6 mg/dL, and PLA2R Ab 787 RU/mL. Renal biopsy showed immune complex-mediated glomerulopathy with positive PLA2R, consistent with primary MN stage II-III. Glomerular basement membrane deposits were strongly positive for IgG4. Electron microscopy showed numerous subepithelial and occasional intramembranous electron-dense immune-type deposits. She was treated with lisinopril and furosemide followed by rituximab in May 2021. Prior to rituximab PLA2R Ab was 342 RU/mL and UPCR was 8671 mg/g Cr. Discussion: There is insufficient data on the risk of flare after COVID-19 vaccine in glomerular diseases. There have been a few case reports of primary MN and minimal change disease after COVID-19 vaccine as well as MN after influenza vaccine. Our case of primary MN flare after COVID-19 vaccine adds support to a potential association between SARS-CoV-2 antigens and loss of tolerance to the PLA2R antigen. Close follow-up of patients with primary MN and other glomerular diseases after COVID-19 vaccination is warranted.