GPA – 10/1/18

Yours truly presented a case of a middle-aged woman with a recent history of otitis, sore throat, conjunctivitis, photophobia, and arthralgias who presented with chronic and progressive decline in functional status and AMS, found to be uremic with work up revealing c-ANCA associated ESRD.


Clinical Pearls

  • Remember that oval fat bodies are specific for glomerular pathology (more commonly nephrotic syndrome but can be seen in nephritic disease as well).
  • ANCA-associated vasculitides include GPA, MPA, eGPA (and renal-limited vasculitis).
  • All have similar features on renal histology (focal necrotizing, crescentic, pauci-immune glomerulonephritis).
  • They can affect multiple organ systems (see breakdown below) which makes their clinical diagnosis challenging apart from the following differences:
    • c-ANCA is associated with GPA, p-ANCA is seen in MPA and eGPA
    • Granulomas are seen in GPA and eGPA
    • Eosinophilia and asthma are associated with eGPA

ANCA-associated vasculitides

Capture

Chart above adapted from this paper by Koldingsnes et al.

Granulomatosis with polyangiitis (GPA)

Diagnostic criteria (two or more has 88% sensitivity and 92% specificity):

  • Nasal or oral inflammation (painful/painless oral ulcers, or purulent or bloody nasal discharge)
  • Abnormal chest radiograph showing nodules, fixed infiltrates, or cavities
  • Abnormal urinary sediment (microscopic hematuria w/w/o red cell casts)
  • Granulomatous inflammation on bx of artery or perivascular area

Clinical presentation:

  • Most commonly in older adults, M=F
  • More common among white individuals (~89%)
  • S/s
    • Fatigue, fever, weight loss, arthralgias, rhinosinusitis, cough, dyspnea, urinary abnormalities, purpura, and neurologic dysfunction.
    • ENT
      • 90% of GPA cases, only 35% of MPA
      • Nasal crusting, sinusitis, otitis media, earache, polychondritis, ulcers, discharge
      • Conductive and/or sensorineural hearing loss
      • Saddle nose deformity
    • Tracheal and pulmonary disease
      • Airways or parenchyma
    • Renal
      • ~18% at presentation but subsequently develops in 77-85% of patients within the first 2 years of disease onset
      • High risk of progression to ESRD
      • Asymptomatic hematuria
      • Subnephrotic range proteinuria
      • Rapidly progressive GN
    • Cutaneous
      • ~50% of patients
      • Leukocytoclastic angiitis is most common which causes purpura of lower extremities
      • Other findings: urticarial, livedo reticularis, nodules, erythema nodosum, pyoderma gangrenosum, and Sweet syndrome
    • Ophthalmic/orbital
      • Conjunctivitis, corneal ulcers, episcleritis/scleritis, optic neuropathy, retinal vasculitis, and uveitis.
    • Other organs
      • CNS: neuropathy, CN abnormalities, mass lesions, hearing loss, granulomatous inflammation of the CNS
      • GI tract, heart, lower GU, parotids, thyroid, liver, or breast
      • High incidence of DVT (unclear mechanism)
    • Can progress slowly over months or explosively over days
    • Relapses can manifest differently than original presentation

Diagnosis requires biopsy!

Treatment:

  • Prompt initiation of therapy can be life and organ sparing
  • Induction therapy: Steroids +-Cyclophosphamide +-Rituximab
  • Maintenance therapy: multiple options-Azathioprine, MTX, Rituximab, Leflunomide

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