WEGENER’S GRANULOMATOSIS is a systemic vasculitis which most commonly involves the upper and lower respiratory tract and kidneys and less commonly the eyes, joints, skin, neurologic, cardiac and gastrointestinal tissues. The disease was first described in 1931 and 1936 by H. Klinger and F. Wegener, respectively.

ETIOLOGY: The cause of Wegener’s granulomatosis is not yet known. Granuloma formation, altered immune reactivity, immune complex deposition, and altered cellular immune responses are believed to play significant roles. There may be a genetic predisposition. [1]

INCIDENCE: In the United States, the disease frequency is approximately 1 in 30,000, with mean age of onset of 40, equal prevalence in men and women, and increased prevalence in whites. Old data indicated that the disease was rare in children and that children accounted for only 0.1% of cases, but the most recent NIH data demonstrates that children and adolescents account for approximately 15% of affected individuals. [2]

PATHOLOGY: The classic histopathology in Wegener's granulomatosis is necrotizing granulomatous vasculitis involving small arteries and veins, most reliably found on biopsies of the lung. Upper respiratory tract biopsies, including the nasal septum, sinus, and trachea, most often show non-specific acute and chronic inflammation with or without giant cells and generally without true vasculitis. Renal biopsies typically show focal segmental glomerulonephritis, with crescent formation and necrosis in more severe forms.

CLINICAL MANIFESTATIONS: The spectrum of clinical features and organ system involvement in Wegener's granulomatosis is broad. As a multisystem disorder predominantly involving the upper and lower respiratory tracts and the kidneys, clinical manifestations vary from "classic," with sinusitis, serous otitis media, rhinitis with nasal ulcerations, cough, hemoptysis, and constitutional symptoms, to "fulminant," with rapidly progressive renal failure and respiratory failure requiring intensive care unit management, to "mild," with arthralgias, polymyalgia rheumatica-type symptoms, or inflammatory eye disease as examples. [1]

Sinusitis is present at initial presentation in about one half to two thirds of patients with Wegener's granulomatosis and is seen in 85 percent of cases during the entire course of disease. A computed tomographic scan of the sinuses is often anatomically more informative than are plain radiographs, especially in the setting of destructive and erosive bone changes.

Although laryngotracheal disease in Wegener's granulomatosis may be asymptomatic, clinical presentations may range from subtle hoarseness to stridor and life-threatening upper airway obstruction. The most characteristic lesion is that of subglottic stenosis, which occurs in up to 16 percent of patients. In pediatric and adolescent patients with Wegener's granulomatosis, the frequency of subglottic stenosis is dramatically increased, reaching an alarming 48 percent. Direct laryngoscopy may reveal active erythematous, friable mucosa or bland scar. Tracheal tomograms, computed tomographic scans, and magnetic resonance imaging may be useful adjuncts in the diagnosis of subglottic stenosis. Only 20 percent of lesions diminish with immunosuppressivetherapy alone, whereas 80 percent are fixed or irreversible owing to chronic fibrosis. [2]


DIAGNOSIS: in the past 15 years, c-ANCA and its relationship to Wegener's granulomatosis have been studied. Clearly, this test is helpful in Wegener's granulomatosis, particularly during active generalized disease, and may be confirmatory. Because reports of false positives are increasing and because sensitivity varies from 30 to 90% in a clinician's diagnosis of Wegener's granulomatosis, depending on the extent of disease and disease activity level, the test cannot be used as a sole diagnostic criterion for Wegener's granulomatosis. Radiologic imaging studies are helpful in diagnosing Wegener's granulomatosis, including chest and sinus radiographs and computed tomography. The differential diagnosis is quite broad and depends on the patient's signs and symptoms. When the classic triad of involvement occurs, with confirmatory tissue biopsy and a positive c-ANCA, the diagnosis is easy. When the process is early and/or limited to the upper airway or kidney, the diagnosis is clinically challenging. [1]

RADIOGRAPHIC FINDINGS: Imaging studies of the paranasal sinuses may reveal characteristic findings in patients with Wegener's granulomatosis. Plain film findings include mucosal thickening, opacification, air-fluid levels, and bony sclerosis or frank obliteration . Computed tomographic findings include bilateral sinus opacification, orbital mass, bone erosion, septal perforation, and mucosal thickening [3]

Tracheobronchial involvement by Wegener’s manifests on CT as mural thickening and narrowing of involved airways. 90% of inflammatory lesions are located in the subglottic region with circumferential tracheal involvement and narrowing occur with a length of involvement ranging from 5 to 45 mm.

On CT, the most common finding of pulmonary Wegener’s is multiple irregularly marginated nodules, which can range from 2 to 20 in number and from 2 to 90 mm in size. Areas of opacification ranging from ground-glass attenuation to frank consolidation are the second most common CT pattern of pulmonary Wegener’s and often represent findings of pulmonary hemorrhage . [4]

TREATMENT: Treatment depends on the severity and location of the disease. A multidisciplinary approach is often needed. Glucocorticoids and cyclophoshamide are the primary medications used for treatment. Combination therapy with oral daily cyclophophamide and glucocorticoids is considered the standard therapy. Methotrexate at times is used as an alternative to cyclophosphamide. Surgical treatment is often required to treat sinus disease, tracheal disease, and less frequently to provide renal transplant.

PROGNOSIS: Whereas Wegener's granulomatosis was once an invariably fatal disease, the combination of cyclophosphamide and prednisone has provided remission in 75% of all patients and improvement in 90%, as evidenced in the National Institutes of Health (NIH) series of long-term follow-up studies. However, relapses occur in at least 50% of those achieving remission at any time from several months to 15 to 20 years after stopping cytotoxic therapy. [2]