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, usually directed against proteinase-3 (less commonly against myeloperoxidase present in severe, active disease) (90% of patients)

• Tissue biopsy usually necessary for diagnosis

General Considerations

• The disease presents as vasculitis of small arteries, arterioles, and capillaries, necrotizing granulomatous lesions of both upper and lower respiratory tract, and glomerulonephritis

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

• Lower respiratory tract symptoms develop in 60% of patients

• Some patients develop both upper and lower respiratory tract symptoms

• Upper respiratory tract symptoms can include

  • Nasal congestion

  • Sinusitis

  • Otitis media, mastoiditis

  • Inflammation of the gums

  • Stridor due to subglottic stenosis

• 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 sinusitis

• Goodpasture disease

• Systemic lupus erythematosus

• Sarcoidosis

• Cocaine use

Diagnosis

Laboratory Tests

• c-ANCA

  • Caused by antibodies to proteinase-3, a constituent of neutrophil granules

  • Has a high specificity (> 90%)

  • In the setting of active disease, the sensitivity of c-ANCA is also reasonably high (= 70%)

• p-ANCA

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

  • Approximately 10–25% of patients with classic granulomatosis with polyangiitis have p-ANCA

• If kidney involvement is present

  • There is proteinuria

  • The urinary sediment contains red cells (with or without white cells) and red cell casts

Imaging Studies

• Chest CT is more sensitive than chest radiograph for infiltrates, nodules, masses, and cavities

• Pleural effusions are uncommon

Procedures

• ANCA testing does not eliminate the need in most cases for confirmation of the diagnosis ...