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Introduction: IgA nephropathy (IgAN) is an immune complex glomerulonephritis (GN) characterized by glomerular deposition of IgA-dominant immune complexes, often accompanied by mesangial hypercellularity. Antineutrophil cytoplasmic antibodies (ANCAs) cause small-vessel vasculitis and pauci-immune crescentic GN. The coexistence of ANCAs and IgAN is quite rare. ANCAs have been associated with inflammatory bowel disease (IBD) but are more prevalent in ulcerative colitis (~75%) than Crohn's disease (~17%). IBD-associated ANCAs are usually p-ANCA or atypical ANCA rather than c-ANCA. ANCA-associated vasculitis (AAV) can be associated with tumor necrosis factor-alpha inhibitors such as infliximab. We report a rare case of c-ANCA PR3-positive IgAN in a patient with IBD treated with infliximab who presented with proteinuria. Case Description: A 27-year-old female with history of Crohn's disease since 2010 treated with infliximab, allergic rhinoconjunctivitis, mild asthma, erythema nodosum in June 2021 (resolved with prednisone), Charcot-Marie-Tooth disease, psoriasis, and COVID-19 disease in Oct 2021, was found to have positive c-ANCA (1:160) and PR3 (5.0 AI, reference <1.0) in Dec 2021, raising question of vasculitis. Her rhinosinusitis was well controlled with allergy medications without oral steroids. She was referred to Nephrology for proteinuria with urinalysis (UA) in April 2022 showing 2+ protein, 3+ blood, 2-10 WBC, 20-50 RBC. Urine protein/creatinine ratio was 1.9. She had foamy urine but no gross hematuria. She previously had UA with packed RBC in June 2021. Urogram showed non-specific bladder wall thickening. Cystourethroscopy was negative. In April 2022, her BP was 97/66 and she had no edema. A renal biopsy in May 2022 revealed IgAN (M0 E1 S1 T0 C0). She was started on lisinopril and fish oil. Discussion(s): This is a very rare case of c-ANCA PR3-positive IgAN in IBD treated with infliximab. The patient's history of sinusitis along with c-ANCA PR3 antibody positivity suggested possibly an AAV associated with infliximab, which has been reported rarely in IBD. Her proteinuria of 1.9 g/day raised concern for GN due to pauci-immune AAV. However, renal biopsy showed IgAN rather than AAV. This case highlights the importance of renal biopsy in establishing a definitive diagnosis of glomerular disorders in patients with ANCA positivity, as serum ANCAs do not necessarily represent pauciimmune GN.
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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.