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 ...