Granulomatosis with Polyangiitis (GPA, formerly called  Wegener's granulomatosis) is a systemic necrotizing granulomatous vasculitis, typically involving the upper and lower respiratory tracts and kidneys.34 The incidence of the disease is not well established but is reported at approximately 0.4 cases per 100,000 population.35 The usual age of onset is 30 to 40 years, but it can start at any age. Men are affected more often than women.

The common presenting feature of GPA is sinus pain with purulent or bloody nasal discharge. Nasal mucosal ulcers are common, and nasal septal perforation is a common complication. Respiratory involvement may begin as a cough, with or without hemoptysis and chest pain.36 Renal involvement is prominent and frequently dominates the patient's clinical picture. Glomerulonephritis with proteinuria, hematuria, and red cell casts typically precedes functional renal impairment.

Neurologic involvement has been reported in 30-55% of patients.37-39 Most common is peripheral neuropathy, followed by cranial neuropathy, ophthalmoplegia, stroke, and seizures. Neurologic complications are not considered to represent a major contribution to mortality in this group.

Pathophysiology

GPA is histologically characterized by a necrotizing vasculitis of both small arteries and veins. This is seen in association with intravascular or extravascular granuloma.40 The lungs demonstrate bilateral nodular infiltrates. Renal involvement is characterized by segmental glomerulitis with granuloma formation.

Circulating and deposited immune complexes have been demonstrated in GPA, but their role in pathogenesis of the disease is unclear. The presence of cytoplasmic antineutrophil cytoplasmic antibodies serves as a marker of active disease.40

Neurologic Manifestations

Neurologic manifestations have been reported in up to 55% of GPA patients, but in a recent series of 324 cases, 33.6% of patients experienced neurologic complications.36-39 The most frequent complication was peripheral neuropathy, occurring in 16% of patients in that series. As many as 28.6% were affected in another.39 Mononeuropathy multiplex predominates.

Cranial neuropathies have been reported in up to 11.7% of patients with GPA,36 with the ophthalmic nerve most often affected. The other commonly affected cranial nerves were the abducens and facial nerves.37

Strokes are considered rare events in GPA. When they occur, they are thought to be related to a cerebral vasculitis.34 Large and small arteries, as well as venous structures, are probably involved.39 Other features of cerebral vasculitis, such as confusion, encephalopathy, and seizure, also have been documented.37

Seizures are also considered rare in GPA, occurring in only 2-3% of cases. They are believed to be associated with the cerebral vasculitis that occurs as a complication of the disease, often as a preterminal occurrence.37

Diagnosis

The diagnosis of GPA is made on the basis of the clinical signs and symptoms described above. Presentation with neurologic manifestations has not been described. Finding necrotizing granulomatous vasculitis on a biopsy of involved tissue secures the diagnosis.

Lymphomatoid granulomatosis is an infiltrative disorder with clinical signs and symptoms that might be confused with GPA. The biopsy findings of GPA and seropositivity for cytoplasmic antineutrophil cytoplasmic antibodies help to differentiate the two.

Treatment

The treatment of choice for GPA is oral cyclophosphamide, usually with the addition of oral prednisone.36-40 After remission, cyclophosphamide is usually replaced with methotrexate or azathioprine, which is continued for a year or two.109

Management of seizures and other neurologic complications depends on control of the underlying inflammatory disorder.

Prognosis

Before the routine use of cyclophosphamide for GPA, the disease was universally fatal within several months. Using current treatment regimens, complete remission is reported as high as 93%.36 The disease recurs in about half of patients but most can expect long-term survival.

Adapted from: Seiden L and Krumholz A. Inflammatory noninfectious disorders. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;135-154.
With permission from Elsevier (www.elsevier.com).

Reviewed and revised March 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

Authored By: 
L Seiden
A Krumholz
Steven C. Schachter, MD
I<
Authored Date: 
03/2004
Reviewed By: 
Steven C. Schachter, MD
on: 
Wednesday, March 31, 2004