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
    • Erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) – usually elevated
  • 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  • Relapses are common, especially if maintenance treatments are fully withdrawn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

   
Sedimentation Rate, Westergren (ESR) 0040325
Method: Visual Identification

Initial evaluation for suspected vasculitis

   
C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Initial evaluation for 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