Granulomatosis with polyangiitis (GPA) necrotizing granulomatous vasculitis

By SWA

Explaining: New onset granulomatous with polyangiitis in a Covid-19 patient: A case report

Granulomatosis with Polyangiitis (GPA), previously known as Wegener’s granulomatosis, is a rare systemic autoimmune disease characterized by necrotizing granulomatous inflammation and vasculitis that primarily affects small to medium-sized blood vessels. This condition typically involves the upper respiratory tract, lungs, and kidneys, but it can also affect other organs.

Pathophysiology:

  1. Necrotizing Granulomatous Inflammation:

    • Granulomas form as part of the immune system's abnormal response to a perceived insult, usually without a clear infectious cause.
    • These granulomas consist of macrophages, T cells, and giant cells, and they are often surrounded by areas of necrosis (tissue death).

  2. Vasculitis:

    • Vasculitis in GPA causes inflammation and destruction of small to medium-sized blood vessels, leading to impaired blood flow, tissue ischemia, and damage to affected organs.
    • This is mediated by an autoimmune response, where anti-neutrophil cytoplasmic antibodies (ANCAs), particularly proteinase-3 (PR3-ANCA), play a significant role in triggering neutrophil activation and vessel inflammation.

Key Features of GPA:

  • Upper Respiratory Tract:

    • Chronic sinusitis, nasal ulcers, epistaxis (nosebleeds), and nasal septal perforation are common.
    • “Saddle nose deformity” may occur due to cartilage destruction.

  • Lungs:

    • Pulmonary involvement includes necrotizing granulomas in the lung tissue, causing nodules (which may cavitate), hemoptysis (coughing up blood), and dyspnea (shortness of breath).

  • Kidneys:

    • The condition often leads to necrotizing glomerulonephritis, causing hematuria, proteinuria, and potentially rapidly progressive renal failure.
    • Kidney involvement is often silent initially but can lead to significant morbidity if untreated.

  • Other Organs:

    • GPA can involve the skin (purpura), eyes (scleritis, uveitis), peripheral nerves (mononeuritis multiplex), joints (arthritis), and other organs.

Diagnosis:

  • Clinical Suspicion:

    • Symptoms involving the respiratory tract, lungs, and kidneys should raise suspicion, especially if systemic symptoms like fever, weight loss, and fatigue are present.

  • Laboratory Tests:

    • Positive c-ANCA (PR3-ANCA) is highly suggestive of GPA.
    • Elevated inflammatory markers (ESR, CRP) and evidence of kidney dysfunction (e.g., elevated creatinine, abnormal urinalysis) may also be seen.

  • Imaging:

    • Chest X-rays or CT scans may reveal lung nodules, cavities, or infiltrates.
    • Sinus CT scans can show mucosal thickening or bone destruction.

  • Tissue Biopsy:

    • The definitive diagnosis requires biopsy of affected tissue (e.g., from the lung, kidney, or nasal passages) showing necrotizing granulomatous inflammation and/or vasculitis.

Treatment:

  • Induction Therapy:

    • High-dose glucocorticoids (e.g., prednisone) combined with an immunosuppressant such as:
      • Rituximab (a monoclonal antibody targeting B cells) or
      • Cyclophosphamide (a cytotoxic agent).

  • Maintenance Therapy:

    • Once remission is achieved, maintenance therapy with azathioprine, methotrexate, or rituximab is used to prevent relapse.

  • Plasma Exchange:

    • May be used in severe cases, such as rapidly progressive glomerulonephritis or diffuse alveolar hemorrhage.

Prognosis:

  • Without treatment, GPA is often fatal due to kidney or lung involvement.
  • With prompt diagnosis and treatment, remission is achievable in most cases, but relapses are common, and long-term follow-up is essential.

Key Points:

  • GPA is a necrotizing granulomatous vasculitis involving multiple organs, with the most common triad being the respiratory tract, lungs, and kidneys.
  • It is strongly associated with c-ANCA/PR3-ANCA, which aids in diagnosis.
  • Early recognition and aggressive immunosuppressive therapy can significantly improve outcomes.

 

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right.
Library of Congress Card Number: LCN 00-192742
ISBN: 0-9703195-0-9

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