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Key Clinical Updates in Granulomatosis with Polyangiitis

American College of Rheumatology/Vasculitis Foundation recommendations favor rituximab as first-line induction therapy. Cyclophosphamide may also be used for induction therapy. Avacopan is FDA-approved as add-on treatment for severe ANCA-associated vasculitis induction therapy in combination with rituximab or cyclophosphamide plus corticosteroids.

For nonsevere disease without life- or organ-threatening manifestations, methotrexate up to 25 mg oral or subcutaneous weekly, plus corticosteroids may be effective induction therapy.

Rituximab, dosed at a fixed interval of 1 g every 6 months or 500 mg every 4 months, is favored as first-line maintenance treatment.

Chung SA et al. Arthritis Rheumatol. [PMID: 34235894]

Jayne DRW et al; ADVOCATE Study Group. N Engl J Med. [PMID: 33596356]

ESSENTIALS OF DIAGNOSIS

  • Classic triad of upper and lower respiratory tract disease and glomerulonephritis.

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

  • Kidney disease is 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

Granulomatosis with polyangiitis (formerly Wegener granulomatosis), which has an estimated incidence of approximately 12 cases per million individuals per year, is one of three vasculitides associated with ANCA. The other “ANCA-associated vasculitides” include microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. Granulomatosis with polyangiitis is characterized by vasculitis of small arteries, arterioles, and capillaries, necrotizing granulomatous lesions of both upper and lower respiratory tract, glomerulonephritis, and other vasculitic organ manifestations. Without treatment, generalized disease is invariably fatal, with most patients surviving less than 1 year after diagnosis. It occurs most commonly in the fourth and fifth decades of life and affects men and women with equal frequency.

CLINICAL FINDINGS

A. Symptoms and Signs

The disorder usually develops over 4–12 months. Upper respiratory tract symptoms develop in 90% of patients and lower respiratory tract symptoms develop in 60% of patients; some patients may have both upper and lower respiratory tract symptoms. Upper respiratory tract symptoms can include nasal congestion, sinusitis, otitis media, mastoiditis, inflammation of the gums, or stridor due to subglottic stenosis. Since many of these symptoms are common, the underlying disease is not often suspected until the patient develops systemic symptoms, or the original problem is refractory to treatment. The lungs are affected initially in 40% and eventually in 80%, with symptoms including cough, dyspnea, and hemoptysis. Other early symptoms can include a migratory oligoarthritis with a predilection for large joints; a variety of symptoms related to ocular disease (unilateral proptosis from orbital pseudotumor; red eye from scleritis [Figure 20–8] (eFigure 20–27), episcleritis, anterior uveitis, or peripheral ulcerative keratitis); purpura or other skin lesions; and dysesthesia due to neuropathy. Renal involvement, which develops in three-fourths of the cases, may be subclinical until kidney disease is advanced. Fever, malaise, ...

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