Wegeners granulomatosis is a disease of unknown etiology that always involves die lungs or upper airways. In 85 percent of cases, the kidneys are affected by glomerulonephritis. The histopathologic diagnosis of Wegeners disease requires demonstration of both necrotizing granulomas and vasculitis. Open lung biopsy is usually performed in suspected disease because it is believed that a large sample of lung is needed both to demonstrate granulomatous vasculitis and to rule out other disease. Trans-bronchial lung biopsy is a less morbid procedure than open lung biopsy, but there is little information published about its usefulness in the diagnosis of this disease. We performed transbronchial biopsies through the fiberoptic bronchoscope in a patient with cavitary lung disease and obtained tissue diagnostic of Wegeners granulomatosis.
A 71-year-old woman had a two-month history of episcleritis, nonproductive cough, dyspnea on exertion, and a five-pound weight loss. There was one episode of scant hemoptysis and, two days prior to admission, she experienced prolonged epistaxis. Her physician found a large right upper lobe cavity on chest roentgenogram and referred her to Vanderbilt University Medical Center for evaluation. She had stopped smoking 20 years ago after approximately a 20 pack-year exposure. TWo of her sisters had had tuberculosis. She previously had a positive PPD (5 TU) skin test and a chest roentgenographic examination showing bilateral apical capping.
Her temperature was 99.4°F, pulse rate was 92/min, and respiratory rate was 24/min. Her blood pressure was 140/65 mm Hg. Bulbar conjunctiva were injected, and cheimosis was present. Lungs were clear to auscultation and resonant to percussion. There was no digital clubbing, and results of the remainder of the physical examination were normal.
Her hematocrit was 35 percent Arterial blood gas values on room air were pH 7.49, Pco, 34 mm Hg, and Pot 70 mm Hg. Serum creatinine level was 3.0 mg/dl, and BUN was 38 mg/dl. Microscopic urinalysis showed 75-100 RBCs, 1-3 WBCs, and few granular casts per high power field. There was 2+ albuminuria. The chest roentgenographic examination revealed a solitary 9×9 cm thick-walled cavity in the right upper lobe (Fig 1). Paranasal sinus films appeared normal. We performed transbronchial biopsies of the right upper lobe cavity under fluoroscopic guidance without complication; four samples of lung tissue were obtained. The serum creatinine and BUN levels rose to 6.5 mg/dl and 54 mg/dl, respectively, and a percutaneous renal biopsy was done.
Two of the four lung tissue specimens demonstrated small pulmonary artery with lumenal occlusion by granulomatous inflammatory infiltrate composed of lymphocytes, macrophages, plasma cells, and giant cells. The vessel wall was focally necrotic with disruption of the internal elastic lamina (Fig 2A and B). Special stains were negative for mycobacteria and fungi. Kidney glomeruli showed focal segmental necrosis with associated crescent formation. Renal tubules and vessels were unremarkable. Immunofluorescent studies of the kidney for immunoglobulin, C3, and C4 gave negative results. Electron microscopy did not reveal electron-dense deposit along the glomerular basement membrane.
The patient was given therapy with intravenous methylpred-nisolone, 10 mg/kg daily for three days, then oral prednisone, 1.0 mg/kg/day. Cyclophosphamide, 3 mg/kg, was administered by mouth. Oliguria developed in the second hospital week, and the patient required dialysis for congestive heart failure.
Untreated Wegeners granulomatosis carries a 90 percent mortality rate over two years; however, specific therapy with cyclophosphamide has been reported to induce remission in over 90 percent of cases. Early treatment is extremely important to prevent renal failure. Since cyclophosphamide therapy has major potential toxicity, a definitive diagnosis should be established before initiating therapy.
The diagnosis of Wegeners granulomatosis requires clinical evidence of disease in two of the three major areas affected; namely, upper airways, lung, and kidney. Biopsies should show granulomas and vasculitis. Upper airway biopsy shows nonspecific inflammation, granulomas, or vasculitis, rarely demonstrating the latter two together. Percutaneous renal biopsy seldom reveals either granulomas or vasculitis. Open lung biopsy is the most sensitive method for obtaining tissue, since it shows necrotizing granulomatous vasculitis in approximately 70 percent of cases.
The chest roentgenogram reveals abnormality in 94 percent of patients with Wegeners granulomatosis. The most common finding is multiple, bilateral nodules ranging in size from several millimeters to 9 centimeters. The nodules cavitate in one-third to one-half of cases, and the cavities are thick-walled with an irregular inner surface. The size of the cavity in our patient was unusual, but not unreported.
There is little published information about transbronchial biopsy in Wegeners granulomatosis. Pinching et al found granulomas and vasculitis on transbronchial biopsy in two of seven patients in their series. They did not comment on whether the radiographic pattern correlated with success or failure of the biopsy. We found granulomatous vasocentric necrotizing inflammation on transbronchial biopsies from the periphery of an upper lobe cavity in our patient, and specific therapy was begun promptly. Unfortunately, our patient developed fulminant renal failure that was unresponsive to cyclophosphamide and corticosteroids.
Although open lung biopsy is the accepted standard, transbronchial lung biopsy has a role in the diagnostic evaluation of Wegeners granulomatosis. The chest roent-genographic examination reveals abnormality in over 90 percent of cases and can define the site for transbronchial biopsy. Using both elastic and special stains, the angiocentric and noninfectious nature of Wegeners disease may be demonstrated. Transbronchial lung biopsy is a less morbid procedure than open lung biopsy. Therefore, transbronchial lung biopsy should be considered as the first attempt to obtain tissue in a patient with pulmonary disease and suspected Wegeners granulomatosis.
Figure 1. The posterior-anterior chest roentgenogram shows a large solitary cavity in the right upper lobe.
Figure 2A (upper). Photomicrograph of the transbronchial lung biopsy tissue. Small pulmonary artery with obliteration of the lumen (small arrow) and focal disruption of the elastic lamina (large arrow) (elastic stain 40 X original magnification). 2B (lower). Photomicrograph of the transbronchial lung biopsy tissue. Granulomatous inflammatory reaction in vessel wall composed of mononuclear cells and multinudeate giant cells (hematoxylin and eosin, original magnification, X1000).