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For further information, see CMDT Part 20-20: Granulomatosis with Polyangiitis

Key Features

Essentials of Diagnosis

  • Triad of

    • Upper respiratory tract disease

    • Lower respiratory disease

    • Glomerulonephritis

  • Suspect if upper respiratory tract symptoms (eg, nasal congestion, sinusitis) are refractory to usual treatment

  • Kidney disease often rapidly progressive

  • Venous thromboembolism commonly occurs

  • ANCAs (90% of patients), usually directed against proteinase-3 (but may be directed against myeloperoxidase)

  • Tissue biopsy usually necessary for diagnosis

General Considerations

  • Presents as vasculitis of small arteries, arterioles, and capillaries, necrotizing granulomatous lesions of both upper and lower respiratory tract, glomerulonephritis, and other vasculitic organ manifestations

  • One of three "ANCA-associated vasculitides" (the others being microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis)

Demographics

  • Annual incidence of 12 per million

  • Occurs most commonly in the fourth and fifth decades of life

  • Affects men and women with equal frequency

Clinical Findings

Symptoms and Signs

  • Usually develops over 4–12 months

  • Fever, malaise, and weight loss

  • Upper respiratory tract symptoms develop in 90% of patients and can include

    • Nasal congestion

    • Sinusitis

    • Otitis media, mastoiditis

    • Inflammation of the gums

    • Stridor due to subglottic stenosis

  • Lower respiratory tract symptoms develop in 60% of patients

  • Some patients develop both upper and lower respiratory tract symptoms

  • Physical examination can be remarkable for congestion, crusting, ulceration, bleeding, and even perforation of the nasal septum

  • The lung is affected initially in 40% and eventually in 80%, with symptoms including cough, dyspnea, and hemoptysis

  • Renal involvement (75%) may be subclinical until renal insufficiency is advanced

  • Other early symptoms can include

    • Unilateral proptosis (from orbital pseudotumor)

    • Red eye from scleritis

    • Arthritis

    • Purpura

    • Dysesthesia due to neuropathy

  • Destruction of the nasal cartilage with "saddle nose" deformity occurs late

  • Patients are at high risk for venous thrombotic events (deep venous thrombosis, pulmonary embolism)

Differential Diagnosis

  • Polyarteritis nodosa

  • Microscopic polyangiitis

  • Eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome)

  • Chronic infectious sinonasal disease

  • Rheumatoid arthritis

  • Systemic lupus erythematosus

  • Lung cancer

  • Cocaine use

  • IgG4-related disease

Diagnosis

Laboratory Tests

  • Most patients have anemia, mild leukocytosis, and elevated acute-phase reactants

  • ANCA

    • Serum ANCA is very useful in the diagnosis of granulomatosis with polyangiitis (Table 20–7)

    • The two key ANCA subtypes relevant to systemic vasculitis are those directed against proteinase-3 and myeloperoxidase

    • Many patients with "limited" granulomatosis with polyangiitis (often confined to the sinus and upper respiratory tract), are ANCA-negative

  • c-ANCA

    • Caused by antibodies to proteinase-3, a constituent of neutrophil granules (PR3-ANCA)

    • Has a high specificity (> 90%) for granulomatosis with polyangiitis but may, less commonly, be seen in the other ANCA-associated vasculitides

  • p-ANCA

    • Caused by antibodies to myeloperoxidase (MPO-ANCA) and is much less specific than c-ANCA

    • Approximately 10–25% of patients with classic ...

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