POLYARTERITIS NODOSA

Epidemiology/Clinical Manifestations. Polyarteritis nodosa (PAN) was reported by Kussmaul and Maier in 1866 and was the first vasculitis to be described. The definition of PAN has evolved and, in 1994, PAN was separated from microscopic polyangiitis (MPA). As it is now defined, PAN is an exceedingly rare vasculitis with an annual incidence of 2 to 9 cases per million. PAN occurs equally between men and women with the mean age at onset being 40 to 50 years, although PAN can also develop in children. Hepatitis B or C can be associated with a PAN-like vasculitis and a cutaneous-isolated PAN can also occur, all of which are approached differently.

PAN is predominantly a disease of medium-sized arteries in which the most common clinical manifestations are fever, weight loss, and myalgias (>90%), with vasculitis involving the peripheral nerve (80%), gastrointestinal tract (40%-65%), skin (50%), the nonglomerular renal vessels (40%-50%) that may manifest as hypertension, testis (20%), eye (10%), or heart (5%-10%). CNS involvement is much more common in pediatric PAN, occurring in up to 22% of children.

Diagnosis. There are no laboratory studies that are diagnostic of PAN, and the typical findings are that of a systemic inflammatory process with an elevation in acute phase reactants such as ESR and/or CRP. Dye arteriography is often performed to examine the visceral and renal circulation, in which PAN would be suggested by microaneurysms, stenoses, or a beaded pattern reflecting sequential areas of arterial narrowing and dilation. Computed tomography (CT) and magnetic resonance arteriography do not currently have sufficient resolution to visualize the vessels affected by PAN. Biopsies reveal necrotizing inflammation of the medium-sized or small arteries with neutrophils, fibrinoid changes, and disruption of the internal elastic lamina.

Treatment/Prognosis. Patients with immediately life-threatening PAN involving the gastrointestinal tract, heart, or CNS should be treated with cyclophosphamide and glucocorticoids as outlined later for granulomatosis with polyangiitis (Wegener) (GPA). In patients in whom the disease manifestations do not pose an immediate threat to life or major organ function, glucocorticoids alone can be considered as initial therapy, with cyclophosphamide being added in patients who continue to have evidence of active disease or who are unable to taper prednisone. The estimated 5-year survival rate of treated patients with PAN is 88%, with mortality being influenced by disease severity. Relapses occur in 10% to 20% of patients.

GRANULOMATOSIS WITH POLYANGIITIS (WEGENER)

Epidemiology/Clinical Manifestations. GPA is characterized by clinical involvement of the upper and lower respiratory tracts and kidneys with granulomatous inflammation and vasculitis of the small to medium-sized vessels (see Plate 5-49). GPA is estimated to occur in 3 in 100,000 people and is seen equally between men and women. The average age at onset has ranged from 40 to 65 years.

At initial presentation, more than 90% of patients with GPA seek medical attention for upper and/or lower airway symptoms. Sinonasal disease occurs in more than 95% of patients and may result in nasal septal perforation and/or saddle-nose deformity, with 85% developing pulmonary involvement. Glomerulonephritis, which is present in 20% of patients at the time of diagnosis but manifests in 80% along the disease course, can be rapidly progressive and lead to renal failure. GPA can involve almost any organ site, with other prominent features including arthralgias/arthritis (60%-70%), skin (40%-50%), ocular disease (51%), such as episcleritis/scleritis and orbital involvement, peripheral and CNS disease (40%-50%), and subglottic stenosis (20%).