Granulomatosis with Polyangiitis - GPA

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics

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; helpful to rule out infection
    • 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
    • Cytoplasmic staining predominates (positive c-ANCA) directed at Anti-PR3
      • Presence not necessary to diagnose GPA if clinical and histological findings are consistent with 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 using 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  • Relapses are common, especially if maintenance treatments are fully withdrawn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

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, formally 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.

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, cartilage formation (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
  • Neurological – mononeuropathy multiplex, sensorimotor polyneuropathy, seizures, CNS palsies
  • Dermatological – palpable purpura, ulcers, Raynaud phenomena, headache, seizures
  • Limited disease – may occur without evidence of systemic vasculitis
    • ​Most often limited to otorhinolaryngologic involvement
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.

C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

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

Guidelines

American Society for Clinical Pathology. Choosing Wisely - Five Things Physicians and Patients Should Question. An initiative of the ABIM Foundation. [Last revision Feb 2015; Accessed: Jan 2016]

Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013; 65(1): 1-11. PubMed

General References

Akikusa JD, Schneider R, Harvey EA, Hebert D, Thorner PS, Laxer RM, Silverman ED. Clinical features and outcome of pediatric Wegener's granulomatosis. Arthritis Rheum. 2007; 57(5): 837-44. PubMed

Comarmond C, Cacoub P. Granulomatosis with polyangiitis (Wegener): clinical aspects and treatment. Autoimmun Rev. 2014; 13(11): 1121-5. PubMed

Lutalo PM, D'Cruz DP. Diagnosis and classification of granulomatosis with polyangiitis (aka Wegener's granulomatosis). J Autoimmun. 2014; 48-49: 94-8. PubMed

Radice A, Bianchi L, Maggiore U, Vaglio A, Sinico RA. Comparison of PR3-ANCA specific assay performance for the diagnosis of granulomatosis with polyangiitis (Wegener's). Clin Chem Lab Med. 2013; 51(11): 2141-9. PubMed

Seo P. Wegener's granulomatosis: managing more than inflammation. Curr Opin Rheumatol. 2008; 20(1): 10-6. PubMed

Medical Reviewers

Last Update: August 2016