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

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