Granulomatosis with Polyangiitis - GPA

Granulomatosis with polyangiitis (GPA) is an antineutrophil cystoplasmic antibody (ANCA)-associated disorder characterized by vasculitis of small- to medium-sized blood vessels and necrotizing granulomatous inflammation in the upper and lower respiratory tract (Chapel Hill, 2012). GPA, formerly known as Wegener granulomatosis, classically involves a triad of organ systems, including the upper respiratory tract, lungs, and kidneys. However, GPA confined to the head and neck is not uncommon.

Quick Answers for Clinicians

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Diagnosis

Indications for Testing

Persistent upper airway symptoms with other systemic manifestations

Criteria for Diagnosis

  • At least two of the following four criteria (American College of Rheumatology [ACR], 1990)
    • Sinus involvement
    • Lung x-ray with nodules, fixed pulmonary infiltrates, or cavities
    • Urinary sediment with hematuria or red cell casts
    • Granuloma inflammation within the artery or arteriole

Laboratory Testing

  • Nonspecific testing – helpful in excluding other diagnoses or identifying organ dysfunction
    • CBC – may demonstrate anemia, thrombocytopenia; helpful to rule out infection
    • Urinalysis – hematuria, proteinuria common
      • Red blood cell casts often present in fresh urine
    • C-reactive protein (CRP)
  • ANCA
    • Indirect immunofluorescence as initial screen
      • If positive – targeted testing for serine antiproteinase 3 (PR3) and myeloperoxidase (MPO)
    • Result interpretation
      • ANCA presence not necessary for diagnosis if clinical and histological findings are consistent with GPA
      • Anti-PR3 – predominates for GPA
      • Anti-MPO – nonspecific, less commonly associated with GPA

Histopathology

  • Tissue biopsy of involved organ – presence of small artery vasculitis with granulomatous infiltration confirms diagnosis
    • Changes tend to be patchy – highest yield from pulmonary biopsy specimen

Prognosis

ANCA titers do not appear to be predictive of relapse (Comarmond, 2014)

Differential Diagnosis

Background

Epidemiology

  • Incidence – 5-10/million worldwide (Lutalo, 2014)
  • Age (Lutalo, 2014)
    • 55 years (mean age of diagnosis)
    • Peaks in seventh decade
    • Rare in children
  • Sex – M:F, equal (Lutalo, 2014)

​Clinical Presentation

  • Constitutional – weight loss, fever, myalgias, malaise
  • Otorhinolaryngologic – most patients have involvement
    • Otologic – serous otitis media, sensorineural hearing loss
    • Rhinologic – congestion, rhinorrhea, anosmia, sinusitis, septal perforation, ulcers, cartilage weakening (saddleback nose)
    • Laryngeal/tracheal – subglottic or tracheal stenosis
    • Pharyngeal – ulcers, granulomatosis lesions
  • Pulmonary – cough, dyspnea, pulmonary hemorrhage, wheezing
  • Renal – glomerulonephritis, proteinuria, hematuria
    • Less common at diagnosis than upper and lower airway involvement, but develops in most patients during disease course
  • Ophthalmologic – episcleritis, keratitis, uveitis, retinal hemorrhages
  • Cardiovascular – pericarditis, cardiac ischemia, arrhythmias, valvular disease
  • Neurologic – mononeuropathy multiplex, sensorimotor polyneuropathy, seizures, central nervous system palsies
  • Dermatologic – palpable purpura, ulcers, Raynaud phenomena, headache, seizures
  • Limited disease – may occur without evidence of systemic vasculitis
    • ​Most often limited to otorhinolaryngologic involvement

ARUP Lab Tests

Preferred test for evaluation of suspected vasculitis

Preferred reflex panel for the workup of suspected vasculitis

For patients with a history of vasculitis, refer to ANCA with reflex to titer and MPO/PR3 antibodies

Preferred reflex panel for managing patients with a known diagnosis of vasculitis

May be assistive in evaluating suspected vasculitis

For the workup of suspected vasculitis, the preferred panel is ANCA-associated vasculitis profile (ANCA/MPO/PR3) with reflex to ANCA titer

Use to monitor previously established MPO/PR3 antibodies or confirm an indirect fluorescent antibody (IFA) ANCA positive test result

Test does not include ANCA testing by IFA

For ANCA testing, refer to the available panel tests

For the workup of suspected vasculitis, refer to ANCA-associated vasculitis profile (ANCA/MPO/PR3) with reflex to ANCA titer

For patients with a history of vasculitis, refer to ANCA with reflex to titer and MPO/PR3 antibodies

Related Tests

May help in ruling out infectious process

Screen for hematuria, proteinuria, and red blood cell casts

Evaluate for suspected vasculitis

Medical Experts

Contributor

Genzen

Jonathan R. Genzen, MD, PhD
Associate Professor of Clinical Pathology, University of Utah
Chief Operations Officer, Medical Director of Automated Core Laboratory, ARUP Laboratories
Contributor

References

Additional Resources