Granulomatosis with Polyangiitis - GPA

Diagnosis

Indications for Testing

  • Persistent upper airway symptoms with other systemic manifestations

Laboratory Testing

  • Nonspecific testing – helpful in excluding other diagnoses or identifying organ dysfunction
    • CBC – may demonstrate anemia, thrombocytopenia
    • Urinalysis – hematuria, proteinuria common
      • Red blood cell casts often present in fresh urine
    • C-reactive protein (CRP)
  • ANCA – target testing toward two main neutrophil granule components, serine PR3 and myeloperoxidase
    • Presence not necessary to diagnose GPA if clinical and histological findings are consistent with GPA
    • Anti-PR3 predominate – suggests GPA (found in 70-90% of active generalized disease forms [Radice, 2013])
    • Anti-myeloperoxidase – nonspecific; therefore less predictive of GPA

Histology

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

Imaging Studies

  • X-ray  – chest or sinus
  • CT/MRI – more sensitive in identifying small inflammatory lesions

Prognosis

  • Relapses are common, especially if maintenance treatments are fully withdrawn
  • Flare-ups might follow reductions of corticosteroid doses

Differential Diagnosis 

Clinical Background

Granulomatosis with polyangiitis (GPA) is a multi-system disorder characterized by vasculitis of small vessels, necrotizing granulomas and associated with antineutrophil cytoplasmic antibodies (ANCA)(Chapel Hill 2012). GPA 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.

Epidemiology

  • Incidence – 5-10/100,000 worldwide (Lutalo, 2014)
  • Age – 55 years (mean age of diagnosis); peaks in 7th decade
    • Rare in children
  • Sex – M:F, equal

Pathophysiology

  • Circulating neutrophils and monocytes express antineutrophil cytoplasm antibody (ANCA) antigens and proteinase 3 (PR3) on the cell surface for most patients
    • Small percentage generate ANCA directed against myeloperoxidase (MPO)
  • ANCA releases reactive oxygen species and lysosomal enzymes, contributing to inflammation of vessel walls
  • ANCA and PR3 attack the vessels, causing endothelial cell injury and necrotizing inflammation
    • Small to medium vessels (eg, capillaries venules, arterioles, arteries and veins)

Clinical Presentation

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

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

May help in ruling out infectious process

   
Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Screen for hematuria, proteinuria, and RBC casts

   
C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Preferred test for evaluation of suspected vasculitis

   
Anti-Neutrophil Cytoplasmic Antibody with Reflex to Titer and MPO/PR-3 Antibodies 2002068
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay

Initial evaluation for suspected vasculitis

If screen is positive, titer and MPO/PR-3 antibodies testing will be added to aid in antibody determination

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Sedimentation Rate, Westergren (ESR) 0040325
Method: Visual Identification

Evaluate for suspected vasculitis