Wegener Granulomatosis

Posted by Elaine Moore Jul 1, 2006

Wegener granulomatosis (WG) is an autoimmune disorder characterized by an acute necrotizing form of vasculitis (blood vessel inflammation) primarily affecting small and medium-sized blood vessels. The common presentation in WG consists of airway necrotizing granulomas (focal areas of chronic inflammation caused by an immune system reaction), systemic vasculitis and focal glomerulonephritis (inflammation of the kidney's functional units or glomeruli). Blood vessels throughout the body may be affected although WG mainly targets the lower and upper respiratory tract, kidneys and spleen. If the disease doesn't affect the kidneys, it's referred to as limited Wegener granulomatosis. Focal vascular lesions may be seen in the sinuses, nose, throat, lungs, ears, eyes, kidneys, skin, joints, and the central nervous system, including the brain. WG is a variable disease in both severity and in its range of affected organs and symptoms. Some patients with WG experience mild vascular changes and others have severe life-threatening organ damage. Men and women are equally affected, and persons of all ages can develop WG although the peak incidence of WG occurs between the ages of 30 and 50. Caucasians are more likely to develop WG than people of other races.

Symptoms

Typical clinical features of WG include head and neck complaints. Common symptoms include inflamed friable mucosa and ulcerations in the nasopharyngeal tract, septal perforations, saddle nose deformities, chronic nasal congestion, cough, wheezing, ear complaints, oral ulcerations, persistent pneumonitis with bilateral nodular infiltrates, chronic sinusitis, and signs of renal (kidney) disease such as blood in the urine. The severity of these complaints is not related to the appearance of the lesions. Some patients may also present with skin rashes, muscle pains, joint involvement, nerve inflammation affecting one or more organs (mononeuritis and polyneuritis respectively), and fever.

The lesions in WG often contain granulomas (characterized by monocytes and macrophages surrounded by lymphocytes), which may be within, adjacent to or clearly separated from the blood vessel wall. These areas are usually surrounded by an affected zone characterized by giant cells and a white blood cell infiltration, causing the lesions to superficially resemble tubercules. Lesions suspected of being caused by WG must be tested for mycobacteria and fungi to differentiate WG from infectious disease processes. WG must also be differentiated from a similar condition known as lymphomatoid granulomatosis, which also causes pulmonary and renal granulomatous lesions.

Two different distinct types of renal lesions are seen in the kidneys of patients with WG who have kidney involvement. In mild WG and early in the disease process, lesions are seen in the glomeruli. Clotting or thrombosis can be seen in isolated functional glomerular loops causing a focal necrotizing glomerulonephritis. More advanced glomerular lesions are characterized by diffuse or widespread necrosis (cell destruction), proliferations and a crest-type cellular appearance. Patients with glomerular lesions may have mild symptoms of blood and protein in their urine, symptoms that respond well to therapy or they can have a rapidly progressive type of disease causing kidney failure. Untreated, up to 80 percent of patients with WG die within one year.

Treatment

Dramatic improvement is seen in patients treated with corticosteroids or cytotoxic drugs such as cyclophosphamide. About 90 percent of patients with WG show a good response to treatment. At the time of diagnosis patients with WG are usually treated with corticosteroids or cyclophosphamide for 4-6 weeks to control the disease process. The dose is then tapered over the next 6 months. Patients are then kept on a low maintenance dose to prevent disease recurrence. The antibiotic trimethoprim-sulfamethoxazole has also been shown to offer improvement in patients with WG. The prognosis or outlook for patients with WG is best if the disease is treated early before the kidneys are affected.

Diagnosis

WG closely resembles the autoimmune disorder polyarteritis nodosa, which suggests that it may also be related to a hypersensitivity reaction, possibly an inhaled infectious or other environmental agent. However, the specific causes of WG remain unknown. The autoimmune nature of WG is also suggested by the favorable response to immunosuppressant medications and the presence of autoantibodies.

Up to 93 percent of patients with active WG have C-anti-neutrophilic cytoplasmic antibodies (©-ANCA). A positive C-ANCA test result is 80 percent specific for WG. In systemic vascular disease, the test has a 78-100 percent sensitivity and in upper airway disease, the sensitivity is 60-70 percent. Patients with WG also have elevated inflammatory markers, including an elevated erythrocyte sedimentation rate (ESR or sed rate) and an elevated C-Reactive Protein (CRP test). A biopsy of the lesions shows granulomatous change (macrophages and giant cells). Tissue studies may also show microabscess formation and cicatrical scarring.