IgA Nephropathy With c-ANCA Positivity in a Patient With Crohn Disease

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.

Florid cystitis cystica et glandularis mimicking a bladder tumour: A rare case report

Background: An 80 years old male patient presented with urinary retention. He had lower urinary tract symptoms for the last two years. The patient was catheterized and subsequently developed gross hematuria. The patient was COVID- 19 positive. Method(s): The ultrasonography showed bladder wall thickening with bladder mass around the neck. The computerized tomography scan showed heterogeneously enhancing thickening in the left lateral wall of the urinary bladder and was suspected to be neoplastic. There was a suspicious heterogeneously enhancing lesion in the base of the prostate. His serum prostate-specific antigen level was 5.79 ng/ml. His repeated urine cytology for malignant cells was non-diagnostic. Result(s): The patient underwent transurethral resection of bladder tumour (TURBT) and transurethral resection of the prostate (TURPT). The TURBT biopsy showed florid cystitis cystica et glandularis and the TURPT biopsy showed adenomatous hyperplasia. Conclusion(s): The florid cystitis cystica et glandularis mimic a malignancy, and it is, therefore, important to consider it as a differential diagnosis while evaluating catheterized patients with lower urinary tract symptoms.

METASTATIC BLADDER PARAGANGLIOMA WITH UNDERLYING SHDB MUTATION

Introduction Phaeochromocytoma and paraganglioma (PPGL) are rare tumors with up to 40% associated with inherited germline mutations. SHDB mutation is associated with an increased risk of metastasis. Case A 36-year-old male presented with hypertensive emergency. He was diagnosed to have a bladder paraganglioma at age 32 when he presented with hypertensive crisis. Ga-68 DOTANOC PET/CT scan then showed a localized 4.7 x 5.3 cm bladder paraganglioma and he underwent complete surgical resection with resolution of his symptoms. Genetic testing done showed SHDB, deletion (exon 1), heterogenous pathogenic variant. He remained asymptomatic and was lost to follow-up due to COVID-19 until his recent admission. During this admission, he had labile blood pressure with symptoms of palpitations and lethargy. He was found to have a 4.3x elevated urine normetanephrine (1639 ug/day, N<374.7). Metanephrine and 3-methoxytyramine levels were normal. His blood pressure was controlled with phenoxybenzamine 20 mg TDS (1 mg/kg), telmisartan 40 mg OM and carvedilol 25 mg BD with improvement in his symptoms. Subsequent anatomical imaging with CT and functional imaging with Ga-68 DOTATATE showed a small recurrence at the bladder wall with metastatic lesions at the left sacral ala measuring 4.5 x 5.1 cm, and multiple lytic lesions over the spine, ribs and also the left acetabulum with the highest uptake of Ga-68 DOTATATE at the C2 vertebra (SUV max 93). He is now planned for peptide receptor radionuclide therapy (PRRT). SHDB mutation is associated with a higher risk of metastatic disease which has remained unexplained. Treatment for metastatic disease include surgical resection where possible, targeted therapy such as PRRT, meta-iodobenzylguanidine (MIBG) therapy, radiotherapy and also systemic therapy such as chemotherapy and tyrosine kinase inhibitors. Conclusion Patients with PPGL, especially those with SHDB mutation, require monitoring at regular intervals to screen and detect metastasis to reduce mortality and morbidity.