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 often rapidly progressive.
Venous thromboembolism commonly occurs.
ANCAs (90% of patients), usually directed against proteinase-3 (less commonly against myeloperoxidase present in severe, active disease).
Tissue biopsy usually necessary for diagnosis.
Granulomatosis with polyangiitis, which has an estimated incidence of approximately 12 cases per million individuals per year, is the prototype of diseases associated with antineutrophil cytoplasmic antibodies (ANCA). Other “ANCA-associated vasculitides” include microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. Granulomatosis with polyangiitis is characterized in its full expression by vasculitis of small arteries, arterioles, and capillaries, necrotizing granulomatous lesions of both upper and lower respiratory tract, glomerulonephritis, and other 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.
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 20–6], episcleritis, anterior uveitis, or peripheral ulcerative keratitis); purpura or other skin lesions; and dysesthesia due to neuropathy (eFigure 20–18). Renal involvement, which develops in three-fourths of the cases, may be subclinical until kidney disease is advanced. Fever, malaise, and weight loss are common.
Scleritis in a patient with granulomatosis with polyangiitis. (Used, with permission, from Everett Allen, MD, in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H. The Color Atlas of Family Medicine, 2nd ed. McGraw-Hill, 2013.)
Classic granulomatosis with polyangiitis with proptosis, ptosis, and ophthalmoplegia. The condition has remained static for 10 years with the use of corticosteroids and cyclophosphamide. (Reproduced, with permission, from Vaughan DG, Asbury T, Riordan-Eva P [editors]. General Ophthalmology, 15th ed. Originally published by Appleton & Lange. Copyright © 1999 by The McGraw-Hill Companies, Inc.)