Granulomatosis with Polyangiitis - GPA

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)
    • Preferred test to detect inflammatory processes (Choosing Wisely: Thirty Things Physicians and Patients Should Question, 2017; American Society for Clinical Pathology)
    • Usually elevated
    • If CRP not available, order erythrocyte sedimentation rate (ESR)
• 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

• Infectious
  • Mycobacteria spp
  • Fungal (eg, Histoplasma capsulatum)
• Vasculitis
  • Microscopic polyangiitis
  • Antiglomerular basement membrane disease (Goodpasture syndrome)
  • Eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome)
  • Single-organ ANCA-associated vasculitis
• Connective tissue disease
  • Systemic lupus erythematosus
  • Mixed connective tissue disease
  • Sjögren syndrome
• Granulomatous disease
  • Sarcoidosis
  • Lymphomatoid granulomatosis
• Lymphoproliferative disease

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