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Abstract: SA-PO784

Unveiling the Enigma: ANCA-Negative Granulomatosis with Polyangiitis

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Shah, Ali, The Wright Center for GME, Scranton, Pennsylvania, United States
  • Simkhada, Shila, The Wright Center for GME, Scranton, Pennsylvania, United States
  • Shahid, Wajeeha, The Wright Center for GME, Scranton, Pennsylvania, United States
Introduction

Granulomatosis with polyangiitis (GPA) is a systemic inflammation of small to medium blood vessels, often linked with anti-neutrophil cytoplasmic antibodies (ANCAs). Diagnosis can be challenging due to diverse symptoms, potentially delaying treatment. Tissue biopsy typically reveals necrotizing granulomatous inflammation, though about 10-20% of cases lack ANCAs complicating identification.

Case Description

A 78-year-old man with COPD, hypertension, high cholesterol, and psoriasis experienced recurrent upper respiratory symptoms, denying hemoptysis or dyspnea. Despite using antihistamines, he had no relief and sought help from his primary care provider. He also had painless hematuria, leading to a scheduled cystoscopy. His recent blood work, ordered by his showed a decrease in hemoglobin from 11.3 to 9.7, an increase in serum creatinine from a baseline of 1.0 to 4.35, and a decrease in glomerular filtration rate (GFR) to 12 prompting an ER visit. Urinalysis revealed proteinuria at 1+, hematuria at 3+, and a high concentration of red blood cells. Renal ultrasound showed non-obstructive right renal calculi without hydronephrosis. Although his potassium levels remained stable, his creatinine continued to worsen (now 7.1), and his urine output decreased, prompting initiation of hemodialysis. Tests for hepatitis and HIV were negative, as were serum tests for various autoimmune markers including ANCA, PR3, anti-MPO, anti-GBM antibodies, and complement levels. Kidney biopsy revealed pauci-immune glomerulonephritis with circumferential fibrous crescents. He was subsequently treated with high-dose intravenous steroids and rituximab in the setting of ANCA-negative Granulomatosis with polyangiitis.

Discussion

The inflammation seen in GPA prompts an immune response, often leading to high ANCA titres. Around 82–94% of GPA patients are ANCA positive, leaving about 10% ANCA negative. These cases without ANCA are often overlooked. Initial symptoms vary, including sinusitis (67%), pulmonary signs like cough, renal failure, skin/mucous membrane ulcers, and abdominal pain with vasculitis. The diagnosis of GPA includes urinalysis showing red blood cell casts, abnormal chest x-ray, oral/nasal ulcers, and granulomatous inflammation on biopsy. Survival without treatment averages 5 months, with a 20% 1-year survival rate. Treatment involves corticosteroids and immunosuppressants.