Diagnosis

Diagnosis is based on clinical features and investigations:

• clinical presentation
  
  
• blood tests:
  • ESR usually raised
  • platelet count usually raised
  • eosinophilia is not usually a feature, in contrast to polyarteritis nodosa and Churg-Strauss syndrome
    
    
• chest radiology:
  • flitting pulmonary infiltrates
  • bilateral nodules or masses which may cavitate
  • mediastinal or hilar lymphadenopathy is rare
    
    
• urinalysis is a sensitive means of detecting renal involvement, and an active urinary sediment with red blood cells (RBC) and casts indicates glomerular disease
  • serum urea and creatinine may be normal despite active renal disease
  • renal biopsy will serve to confirm the diagnosis and document the extent of renal inflammation or scarring
  • urinalysis is the single most important investigation. The extent of renal impairment and rate of deterioration in renal function is a major determinant of prognosis. The detection of proteinuria and/or haematuria in a patient with a systemic illness mandates immediate further investigation and is a medical emergency (1)
    
    
• histological demonstration of granulomata in the respiratory tract
  
  
• histological examination of the kidney will reveal characteristic focal necrotizing glomerulonephritis:
  • in advanced cases there may be widespread crescent formation around the glomeruli
  • evidence of vasculitic changes in small arterioles, veins and capillaries
• over 90% of patients with Granulomatosis with polyangiitis (GPA) are C-ANCA positive
  • initial screening of all sera by indirect immunofluorescence on ethanol-fixed neutrophils to discriminate 2 main patterns of ANCA: a cytoplasmic pattern (c-ANCA) and a perinuclear pattern (p-ANCA)
  • pattern obtained should then be confirmed by a more specific ELISA test, specifically for antiproteinase 3 and antimyeloperoxidase
  • combined approach of immunofluorescence and ELISA produces sensitivity of 73% and a diagnostic specificity of 99% (2)

The diagnostic criteria, as defined by the American College of Rheumatology for the diagnosis of Wegener's granulomatosis requires at least 2 of the following 4 criteria (3):

(1) oral ulcers or nasal discharge,

(2) the presence of nodules, fixed infiltrate, or cavities on a chest radiograph,

(3) nephritic urinary sediment (red cell cast or >5 red blood cell per high power field),

and (4) granulomatous inflammation on a biopsy

Note though that oral ulceration generally occurs late in the disease (2).

Reference:

1. ARC Autumn 2012. Topical Reviews - ANCA-associated vasculitis; 1:1-12.
2. Ponniah I et al. Wegener's granulomatosis: The current understanding. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005 Sep;100(3):265-70.
3. Rao JK et al. Limitations of the 1990 American College of Rheumatology Classification Criteria in the diagnosis of vasculitis, Ann Intern Med 1998;129: 345-352.