History and Epidemiology

Granulomatosis with polyangiitis1 (GPA) vasculitis is a rare autoimmune disorder that attacks the blood vessels, causing inflammation and damage. It affects approximately three out of every 100,000 people.1 The condition can occur at any age, but it is most commonly diagnosed in Caucasian adults between 40 and 65 years of age.1 GPA vasculitis affects males and females equally, and is rare in children.1

GPA vasculitis was known previously as Wegener granulomatosis, but was renamed after Wegener’s ties to the Nazi party became known in 2000.2 The American College of Rheumatology, the American Society of Nephrology, and The European League Against Rheumatism also recommended renaming Wegener’s granulomatosis with terms that better describe the disease.2

GPA Vasculitis Diagnosis & Presentation

Symptoms of GPA vasculitis may range from mild to life-threatening and may develop quickly (over a few days) or slowly (over a few months).1 Symptoms seen early in the disease can include:3

  • upper respiratory symptoms resembling a cold
  • sinus pain, nasal congestion, and a runny nose
  • nosebleeds
  • hearing loss or ear pain
  • hoarseness
  • feeling short of breath
  • chest pain, persistent cough that may produce bloody sputum

Other symptoms can include:3

  • tear in the nasal septum
  • eye problems, including:
    • conjunctivitis
    • ulceration of the cornea
    • inflammation of the sclera and membrane covering the sclera
  • sores on the skin
  • lack of appetite and weight loss
  • fever
  • fatigue and joint pain
  • night sweats
  • numbness in the limbs, toes, or fingers
  • inflammation and narrowing of the trachea

Among people diagnosed with GPA vasculitis, 75% may develop kidney problems.3 They may be asymptomatic or may present with edema in the legs.3

A diagnosis of GPA vasculitis is based on patient symptoms, history, and various laboratory tests.3

Diagnostic Workup

A diagnosis of GPA vasculitis may be suspected if a positive antineutrophil cytoplasmic antibody (ANCA) is found.3 However, this test may be negative in up to 20% of people with GPA vasculitis.4 Because other diseases may also result in a positive ANCA, diagnosis of GPA ANCA vasculitis must also be based on:

  • symptoms, including oral ulcers or nasal discharge2
  • physical exam
  • other labs, including:2
    • complete blood count
    • electrolytes
    • renal function panel
    • urinalysis showing a certain number of red blood cells or casts
    • erythrocyte sedimentation rate
    • c-reactive protein
  • imaging studies, such as x-ray, CT scan, or MRI4
  • lung function
  • biopsy of affected tissues

Differential Diagnosis of GPA Vasculitis

There are several diseases that should be considered before a diagnosis of GPA vasculitis is reached. These can include:2

  • Autoimmune conditions, such as:
    • rheumatoid arthritis
    • sarcoidosis
    • lupus
    • amyloidosis
  • Infections, including:
    • sepsis
    • disseminated fungal or gonococcal infections
    • endocarditis
    • infections caused by mycobacterium
    • glomerulonephritis caused by Streptococcus pneumoniae.
  • Other types of vasculitis, including:
    • Goodpasture syndrome
    • Churg-Strauss syndrome
    • microscopic polyangiitis
    • ANCA associated vasculitis caused by medications
    • renal limited vasculitis
    • polyarteritis nodosa
    • mixed cryoglobulinemia
    • Henoch Schonlein purpura
  • Malignancies, such as:
    • carcinomatosis (original cancer that becomes widespread in the body)
    • Castleman’s disease (overgrowth of lymph nodes)
    • lymphoma
    • lymphomatoid granulomatosis
  • Drug toxicities, including:
    • levamisole (a medication used to treat parasitic worms in animals that is frequently a contaminant of cocaine)
    • amphetamines
    • cocaine
  • Idiopathic pulmonary alveolar hemorrhage

Management of GPA Vasculitis

Pharmacotherapy

GPA vasculitis treatment is primarily pharmacotherapy and depends on the severity of the disease. Mild GPA vasculitis may be treated with prednisone and methotrexate.1 To induce remission in severe disease, cyclophosphamide plus glucocorticoids may be given.2 Another treatment option for severe disease is rituximab plus corticosteroids.1 Once remission is achieved, methotrexate, azathioprine, or rituximab are used for maintenance. Maintenance therapy may last for 12 to 36 months or longer in patients at higher risk of relapse.2

Other possible treatments include:2

  • mycophenolate mofetil
  • cyclosporine
  • intravenous immunoglobulin (IVIG)
  • trimethoprim-sulfamethoxazole

Tavneos (avacopan), a complement 5a receptor antagonist, was approved by the U.S. Food and Drug Administration in October 2021.1 It may be used as an adjunctive treatment along with steroid treatment.5

GPA vasculitis may affect the kidneys. In severe cases, plasmapheresis, dialysis, or a kidney transplant may be necessary.2 Surgery may be needed to maintain the airway if subglottal stenosis or tracheal stenosis occurs. Patients who develop a saddle nose because of septum perforation may undergo surgery to correct it once they are in remission.3

Patients should be counseled to keep all appointments for check-ups, lab work, and imaging studies.4 Routine follow-up helps prevent complications that may occur due to flare-ups.

Nonpharmacotherapy

Due to the chronic nature of this disease, support groups or individual counseling may prove helpful.1

Monitoring GPA Vasculitis Side Effects

Disease-related complications of GPA vasculitis include:2

  • vision and hearing loss
  • septal perforation, leading to “saddle nose” deformity
  • pulmonary hemorrhage causing respiratory failure
  • end-stage renal disease or chronic kidney disease
  • mononeuritis multiplex (a type of peripheral neuropathy)

Since treatments for GPA vasculitis may suppress the immune system, preventing infection is paramount.2 Patients should be advised to get flu, pneumonia, and shingles vaccines.1

Side effects to watch for with glucocorticoids include:2

Methotrexate monitoring parameters include:2

  • liver toxicity
  • sores and inflammation in the mouth
  • pneumonitis
  • bone-marrow suppression

Along with infection, cyclophosphamide toxicities can include:2

  • myelodysplasia
  • low sodium level
  • bladder cancer and hemorrhagic cystitis
  • gonadal toxicity
  • bone marrow suppression

Patients receiving rituximab should be monitored for:

  • infections
  • progressive multifocal leukoencephalopathy
  • neutropenia
  • infusion reactions

References

  1. Vasculitis Foundation. Granulomatosis with Polyangiitis. (2021). Accessed August 27, 2022.
  2. Garlapati P, Qurie A. Granulomatosis with Polyangiitis. [Updated 2021 Dec 7]. In: StatPearls NCBI Bookshelf version. StatPearls Publishing; 2022. Accessed August 29, 2022.
  3. National Organization for Rare Disorders. Granulomatosis with Polyangiitis. (2020). Accessed August 27, 2022.
  4. American College of Rheumatology. Granulomatosis with polyangiitis (Wegener’s). December 2021. Accessed August 27, 2022.
  5. U.S. Food and Drug Administration. Tavneos (avacopan) capsules, for oral use. October 2021. Accessed August 29, 2022.

Author Bio

Jen Seabright, PharmD, is a freelance medical writer based in Pittsburgh, PA.