Catheterization a n d Cardiovascular Diagnosis 1:329-335 i1 9 7 5 )
WEGENER’S GRANULOMATOSIS: Angiographic Study and Case Report with Prolonged Survival Michael M. Edelstein, M.D., Morton Wexler, M.D., and Ezekiel Freed, M.D. In the limited form of Wegener’s granulomatosis pulmonary arteries were pruned and slightly stretched by a cavitating granuloma. Bronchial and renal vasculature were normal. The microscopic focal small vessel changes are not appreciable at angiography. Therefore, angiography is of no value in establishing the diagnosis of Wegener’s granulomatosis. Key words: angiography. pulmonary, cavitation. pulmonary, granuloma, angiography, vasculitls, Wegener’s granulomatosis
Wegener’s granulomatosis is a disease entity recently segregated from periarteritis nodosa ( I ) , characterized by granulomas of the upper respiratory tract and lungs, diffuse vasculitis of arteries and veins and glomerulitis ( 2 ) . In 1966, Carrington and Liebow differentiated the disease into limited and extensive forms on the basis of the absence or presence of glomerulitis (3). This distinction is valid based on the demonstrated response to steroids and/or immunosuppressants (3-5). There have been several recent reports of success using angiography in establishing diagnoses in the vasculitides (6-8). There is also documentation of abnormal vascularity shown by arteriography in granulomatous disease (9- I I). Because of the reported relationship between Wegener’s granulomatosis and periarteritis nodosa (1,2,5,12,13) and the characteristic angiographic findings in periarteritis nodosa and in pulmonary granulomas, it was felt that arteriography might assist in establishing the diagnosis of Wegener’s granulomatosis. From The Northridge Hospital Foundation, Northridge, California
Reprint requests to: Michael M . Edelstein, M.D., Department of Radiology. Northridge Hospital Foundation, 18300 Roscoe Boulevard, Northridge, California 91 324. Received February 2.5. 1975, revision accepted April 19. 1975
329
0 1 9 7 5 Alan R. Liss, Inc., 150 Fifth Avenue, New Vork, N.Y. 10011
330
Edelstein, Wexler, and Freed
We have recently had the opportunity to perform renal, pulmonary. and bronchial arteriography. and abdominal and thoracic aortography in a patient with the limited form of necrotizing granulomatosis and angiitis. Although there is passing reference to pulmonary arteriography in one case in the literature (4), this is the first report of the angiographic evaluation of Wegener’s granulomatosis. REPORT OF A CASE
The patient is a 56 year old Caucasian male with coronary atherosclerosis and chronic obstructive pulmonary disease. At admission in October, 1971, one month after a trip through Kansas, he had deep ulcers of the tongue with exudate, marked necrosis, and tenderness. There were no other abnormalities. Wedge biopsy of his tongue revealed chronic granulomatous inflammation, without caseation or specific granuloma formation. Stains and cultures for fungi and organisms were negative. The patient improved and was discharged after five days. For three months he was noted to have changing patchy pneumonitis with nonspecific treatment. On 12-27-71, large ulcers were again present on both sides and the dorsum of the tongue. N o lymph nodes were palpable. Moist rates were present over the lower chest. He was cachectic and febrile. Laboratory values included normal CBC and urinalysis. and an elevated ESR. Skin tests showed no reaction. All other extensive testing was negative. Transcricoid bronchial biopsy and bronchography were normal. Bone marrow aspiration and bronchoscopy were not definitive. The patient’s fever and symptoms flared, and dexamethasone was begun with dramatic improvement. X-rays of the sinuses revealed extensive mucoperiostea! thickening in the right maxillary antrum and minimal changes in the left, without osseous destruction. Chest x-ray (Figure I ) showed multiple bilateral shaggy densities, especially in the lower lobes with cavitation of some of the nodules. The location of lesions differed from previous studies, with new cavities and increasing size and number of lesions. At angiography, the thoracic aorta, and intercostal and bronchial arteries were normal. Bilateral fibromuscular dysplasia of the main renal arteries was noted with otherwise normal renal vessels. A selective pulmonary arteriogram demonstrated intrinsically normal pulmonary vasculature. with pruning and straightening of the vessels in the region of a cavitating granuloma (Figure 2): nonadjacent pulmonary arteries were entirely normal. Discontinuance of steroid therapy led to recurrence of symptoms. Steroids were recommenced and symptoms again remitted. Thoracotomy and biopsy of the right lower lobe finally discovered multiple inflammatory nodules. several mm’s to several cm’s in size throughout the lung, but more prominently in the lower lobes. Pathologic evaluation (Figure 3) revealed granulomas with necrotic centers scattered throughout the tissues with no constant relationships to blood vessels. Surrounding the areas of necrosis were aggregates of chronic inflammatory cells
Wegener's Granulomatosis, Angiography
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Fig. 1 Chest x-ray, PA, December 31, 1971 demonstrating multiple shaggy nodules in both lungs; more numerous at the bases with a tendency to confluence. Some of the nodules (arrows) show cavitation.
with some multinucleated giant cells. Several arteries had their walls infiltrated by chronic inflammatory cells. These findings indicated Wegener's granulomatosis. The patient was discharged on 1-20-72. greatly improved. He was placed on a regimen of steroids and Cytoxan and has done well for 3 years without recurrence. DISCUSSION
Wegener's granulomatosis is protean in its manifestations (2-5,14- 16). Ulcerating lesions of the midline oral and pharyngeal tissues, pulmonary granulomas, and renal dysfunction subsequent to glomerulitis are its hallmarks.
332
Edelstein, Wexler, and Freed
Fig. 2 Selective left pulmonary angiogram early midarterial phase. Photographic magnificatlon x 1.5. Straightening and pruning of distal pulmonary arteries in region about a cavitating granuloma. Other pulmonary vessels are normal.
Fig. 3 Photomicrograph x 60, demonstrating area of small vessel vasculitis (-) bordering on granuloma. No vascular fibrinoid necrosis is seen. The vessel contains an inflammatory thrombus (x). Parenchyma is infiltrated by lymphocytes and plasma cells, with border of necrotic tissue (*) surrounded by atelectatic lung.
w W w
334
Edelstein, Wexler, and Freed
The radiographic aspects of the disease (13,15,17,18) include mucoperiosteal proliferation and osseous destruction seen on sinus x-rays. Chest x-rays reveal fleeting, changing pneumonias. shaggy, usually multiple nodules, infiltrates, thin and thick walled cavities and pleural effusions. The practical diagnostic considerations at the patient's last admission were narrowed to histoplasmosis (4,14), midline malignant reticulosis or lymphoma (14,20). and Wegener's granulomatosis (3,12,14,18). Inasmuch as the presence of chronic obstructive pulmonary disease and coronary atherosclerosis inveighed against open lung biopsy, angiography seemed a likely alternative toward establishing the diagnosis. However, our experience indicates that this is not so. The disease process encompasses two distinct elements, interstitial and parenchymal granulomas and a discrete vasculitis. In the limited form, fibrinoid necrosis of vessels is uncommon and granulomas are the major vascular lesion (3,4). Even in the extensive form, said to exhibit the classic changes of periarteritis nodosa (2,21) the vasculitis affects much smaller vessels (3), whereas the arteritis of periarteritis nodosa affects medium sized muscular arteries, especially at vessel branchings (22). Aneurysms are considered the pathognomonic changes of periarteritis nodosa (5,8,22). These changes have not been seen in the vessels in Wegener's granulomatosis (3). Most authors report only a scattered diffuse involvement due either to fibrinoid necrosis o r to granuloma formation (2,3,12,13,22). CONCLUSION
We are faced with vascular alterations not readily demonstrated by angiographic technique, even of selective nature. The vessels are too small, and the changes too scattered o r nonspecific to be diagnostic. Thus, angiography is of no value in establishing the diagnosis of Wegener's granulomatosis. ACKNOWLEDGEMENTS
J.P.M. Black, M.D.. referred the case to us. E. Philip Klein, M.D., kindly reviewed the pathology and prepared the photomicrograph. Ms. S. Latus assisted with the literary search and bibliographic review. REFERENCES I . Wegener F: Ubereine eigenartige rhinogene granulomatose rnit besonderer berteiligung des arterien systemes und der nieren. Beitr Path Anat 102:36-38, 1939. 2 . Godman CG and Churg J : Wegener's granulomatosis. Arch Path 58533-553. 1994. 3. Carrington CB and Liebow AA: Limited forms of angitis and granulomatosis of Wegener's type. Arner J Med 41:497-527, 1966. 4. Israel HL and Patchefsky AS: Wegener's granulomatosis of lung: diagnosis and treatment. Experience with 12 cases. Ann Intern Med 74:881-891, 1971. 5 . McCombs RP: Systemic "Allergic" vasculitis. JAMA 194: 10.59- 1064, 1965. 6 . Casarella WJ et al.: Renal scleroderma: a combined radiological physiological study. Exhibit, ARRS. Washington DC, 1972. 7. Citron BP et al.: Necrotizing angiitis associated with drug abuses. N Engl J Med 283:1003-1011. 1970.
Wegener's Granulomatosis, Angiography
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8. Dornfeld L , Lecky JW and Peter JB: Polyarteritis and intrarenal renal artery aneurysms. JAMA 2 15: 1950- 1952. I97 I . 9. Becker JA: Zanthogranulomatous pyelonephritis. A case report with angiographic findings. Acta Radio. (Diagn) (Stockholm) 4: 139-144, 1966. 10. Goffrini P: Bronchial arterial systems and bronchial arteriography in lung disease. J Cardiovasc Surg (Torino) 8:501-509, 1967. I I . North L B , Boushy SF and Houk V N : Bronchial and intercostal arteriography in non-plastic pulmonary disease. Amer J Roentgen 107:3?8-342. 1969. 12. Levin DC: Pulmonary abnormalities in the necrotizing vasculitides and their rapid response to steroids. Radiol 97:521-.52h. 1970. I ? . Felson B: Less familiar roentgen patterns of pulmonary granulomas. AmerJ Roentgen 8:211-231, 1969. 14. Aach K and Kissane J: Wegener's granulomatosis. Amer J Med 48:496502. 1970. 15. Felson B and Braunstein H: Noninfectious necrotizing granulomatosix. Radiol 70:326-334. 1958. 16. Cassan SM, Coles DT and Harrison EG Jr.: The concept of limited forms of Wegener's granulomatosis. Amer J Med 49:366379. 1970. 17. Hulse R and Jung H: Wegener's granulomatosis in the region of paranasal sinuses and skull base. Roentgenological aspects. Fortshr Roentgen Str I15:561-572. 1971. 18. Smith S R , Smith JW and Theros EG: Wegener's granulomatosis, lymphomatoid variant. Radiol 98:439-444, 1971. 19. Calcaterra TC: Orolaryngeal histoplasmosis. Laryngscope 80: I I I- 170. 1970. 20. Kassel SH. Echevarria RA and Guzzo FD: Midline malignant reticulosis (so-called lethal midline granuloma). Cancer 23:920-935. 1969. 21. Zeek PM. Smith C C and Weeter J C : Studies on periarteritis nodosa I l l . The differentiation between the vascular lesions of periarteritis nodosa and hypersensitivity. Amer J Path 24:899-901, 1948. 2 2 . Leek PM: Periarteritis nodoh critical review. Amer J Clin Path 2 2 : 1952.
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WEGENER’S GRANULOMATOSIS: Angiographic Study and Case Report with Prolonged Survival Michael M. Edelstein, M.D., Morton Wexler, M.D., and Ezekiel Freed, M.D. In the limited form of Wegener’s granulomatosis pulmonary arteries were pruned and slightly stretched by a cavitating granuloma. Bronchial and renal vasculature were normal. The microscopic focal small vessel changes are not appreciable at angiography. Therefore, angiography is of no value in establishing the diagnosis of Wegener’s granulomatosis. Key words: angiography. pulmonary, cavitation. pulmonary, granuloma, angiography, vasculitls, Wegener’s granulomatosis
Wegener’s granulomatosis is a disease entity recently segregated from periarteritis nodosa ( I ) , characterized by granulomas of the upper respiratory tract and lungs, diffuse vasculitis of arteries and veins and glomerulitis ( 2 ) . In 1966, Carrington and Liebow differentiated the disease into limited and extensive forms on the basis of the absence or presence of glomerulitis (3). This distinction is valid based on the demonstrated response to steroids and/or immunosuppressants (3-5). There have been several recent reports of success using angiography in establishing diagnoses in the vasculitides (6-8). There is also documentation of abnormal vascularity shown by arteriography in granulomatous disease (9- I I). Because of the reported relationship between Wegener’s granulomatosis and periarteritis nodosa (1,2,5,12,13) and the characteristic angiographic findings in periarteritis nodosa and in pulmonary granulomas, it was felt that arteriography might assist in establishing the diagnosis of Wegener’s granulomatosis. From The Northridge Hospital Foundation, Northridge, California
Reprint requests to: Michael M . Edelstein, M.D., Department of Radiology. Northridge Hospital Foundation, 18300 Roscoe Boulevard, Northridge, California 91 324. Received February 2.5. 1975, revision accepted April 19. 1975
329
0 1 9 7 5 Alan R. Liss, Inc., 150 Fifth Avenue, New Vork, N.Y. 10011
330
Edelstein, Wexler, and Freed
We have recently had the opportunity to perform renal, pulmonary. and bronchial arteriography. and abdominal and thoracic aortography in a patient with the limited form of necrotizing granulomatosis and angiitis. Although there is passing reference to pulmonary arteriography in one case in the literature (4), this is the first report of the angiographic evaluation of Wegener’s granulomatosis. REPORT OF A CASE
The patient is a 56 year old Caucasian male with coronary atherosclerosis and chronic obstructive pulmonary disease. At admission in October, 1971, one month after a trip through Kansas, he had deep ulcers of the tongue with exudate, marked necrosis, and tenderness. There were no other abnormalities. Wedge biopsy of his tongue revealed chronic granulomatous inflammation, without caseation or specific granuloma formation. Stains and cultures for fungi and organisms were negative. The patient improved and was discharged after five days. For three months he was noted to have changing patchy pneumonitis with nonspecific treatment. On 12-27-71, large ulcers were again present on both sides and the dorsum of the tongue. N o lymph nodes were palpable. Moist rates were present over the lower chest. He was cachectic and febrile. Laboratory values included normal CBC and urinalysis. and an elevated ESR. Skin tests showed no reaction. All other extensive testing was negative. Transcricoid bronchial biopsy and bronchography were normal. Bone marrow aspiration and bronchoscopy were not definitive. The patient’s fever and symptoms flared, and dexamethasone was begun with dramatic improvement. X-rays of the sinuses revealed extensive mucoperiostea! thickening in the right maxillary antrum and minimal changes in the left, without osseous destruction. Chest x-ray (Figure I ) showed multiple bilateral shaggy densities, especially in the lower lobes with cavitation of some of the nodules. The location of lesions differed from previous studies, with new cavities and increasing size and number of lesions. At angiography, the thoracic aorta, and intercostal and bronchial arteries were normal. Bilateral fibromuscular dysplasia of the main renal arteries was noted with otherwise normal renal vessels. A selective pulmonary arteriogram demonstrated intrinsically normal pulmonary vasculature. with pruning and straightening of the vessels in the region of a cavitating granuloma (Figure 2): nonadjacent pulmonary arteries were entirely normal. Discontinuance of steroid therapy led to recurrence of symptoms. Steroids were recommenced and symptoms again remitted. Thoracotomy and biopsy of the right lower lobe finally discovered multiple inflammatory nodules. several mm’s to several cm’s in size throughout the lung, but more prominently in the lower lobes. Pathologic evaluation (Figure 3) revealed granulomas with necrotic centers scattered throughout the tissues with no constant relationships to blood vessels. Surrounding the areas of necrosis were aggregates of chronic inflammatory cells
Wegener's Granulomatosis, Angiography
331
Fig. 1 Chest x-ray, PA, December 31, 1971 demonstrating multiple shaggy nodules in both lungs; more numerous at the bases with a tendency to confluence. Some of the nodules (arrows) show cavitation.
with some multinucleated giant cells. Several arteries had their walls infiltrated by chronic inflammatory cells. These findings indicated Wegener's granulomatosis. The patient was discharged on 1-20-72. greatly improved. He was placed on a regimen of steroids and Cytoxan and has done well for 3 years without recurrence. DISCUSSION
Wegener's granulomatosis is protean in its manifestations (2-5,14- 16). Ulcerating lesions of the midline oral and pharyngeal tissues, pulmonary granulomas, and renal dysfunction subsequent to glomerulitis are its hallmarks.
332
Edelstein, Wexler, and Freed
Fig. 2 Selective left pulmonary angiogram early midarterial phase. Photographic magnificatlon x 1.5. Straightening and pruning of distal pulmonary arteries in region about a cavitating granuloma. Other pulmonary vessels are normal.
Fig. 3 Photomicrograph x 60, demonstrating area of small vessel vasculitis (-) bordering on granuloma. No vascular fibrinoid necrosis is seen. The vessel contains an inflammatory thrombus (x). Parenchyma is infiltrated by lymphocytes and plasma cells, with border of necrotic tissue (*) surrounded by atelectatic lung.
w W w
334
Edelstein, Wexler, and Freed
The radiographic aspects of the disease (13,15,17,18) include mucoperiosteal proliferation and osseous destruction seen on sinus x-rays. Chest x-rays reveal fleeting, changing pneumonias. shaggy, usually multiple nodules, infiltrates, thin and thick walled cavities and pleural effusions. The practical diagnostic considerations at the patient's last admission were narrowed to histoplasmosis (4,14), midline malignant reticulosis or lymphoma (14,20). and Wegener's granulomatosis (3,12,14,18). Inasmuch as the presence of chronic obstructive pulmonary disease and coronary atherosclerosis inveighed against open lung biopsy, angiography seemed a likely alternative toward establishing the diagnosis. However, our experience indicates that this is not so. The disease process encompasses two distinct elements, interstitial and parenchymal granulomas and a discrete vasculitis. In the limited form, fibrinoid necrosis of vessels is uncommon and granulomas are the major vascular lesion (3,4). Even in the extensive form, said to exhibit the classic changes of periarteritis nodosa (2,21) the vasculitis affects much smaller vessels (3), whereas the arteritis of periarteritis nodosa affects medium sized muscular arteries, especially at vessel branchings (22). Aneurysms are considered the pathognomonic changes of periarteritis nodosa (5,8,22). These changes have not been seen in the vessels in Wegener's granulomatosis (3). Most authors report only a scattered diffuse involvement due either to fibrinoid necrosis o r to granuloma formation (2,3,12,13,22). CONCLUSION
We are faced with vascular alterations not readily demonstrated by angiographic technique, even of selective nature. The vessels are too small, and the changes too scattered o r nonspecific to be diagnostic. Thus, angiography is of no value in establishing the diagnosis of Wegener's granulomatosis. ACKNOWLEDGEMENTS
J.P.M. Black, M.D.. referred the case to us. E. Philip Klein, M.D., kindly reviewed the pathology and prepared the photomicrograph. Ms. S. Latus assisted with the literary search and bibliographic review. REFERENCES I . Wegener F: Ubereine eigenartige rhinogene granulomatose rnit besonderer berteiligung des arterien systemes und der nieren. Beitr Path Anat 102:36-38, 1939. 2 . Godman CG and Churg J : Wegener's granulomatosis. Arch Path 58533-553. 1994. 3. Carrington CB and Liebow AA: Limited forms of angitis and granulomatosis of Wegener's type. Arner J Med 41:497-527, 1966. 4. Israel HL and Patchefsky AS: Wegener's granulomatosis of lung: diagnosis and treatment. Experience with 12 cases. Ann Intern Med 74:881-891, 1971. 5 . McCombs RP: Systemic "Allergic" vasculitis. JAMA 194: 10.59- 1064, 1965. 6 . Casarella WJ et al.: Renal scleroderma: a combined radiological physiological study. Exhibit, ARRS. Washington DC, 1972. 7. Citron BP et al.: Necrotizing angiitis associated with drug abuses. N Engl J Med 283:1003-1011. 1970.
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8. Dornfeld L , Lecky JW and Peter JB: Polyarteritis and intrarenal renal artery aneurysms. JAMA 2 15: 1950- 1952. I97 I . 9. Becker JA: Zanthogranulomatous pyelonephritis. A case report with angiographic findings. Acta Radio. (Diagn) (Stockholm) 4: 139-144, 1966. 10. Goffrini P: Bronchial arterial systems and bronchial arteriography in lung disease. J Cardiovasc Surg (Torino) 8:501-509, 1967. I I . North L B , Boushy SF and Houk V N : Bronchial and intercostal arteriography in non-plastic pulmonary disease. Amer J Roentgen 107:3?8-342. 1969. 12. Levin DC: Pulmonary abnormalities in the necrotizing vasculitides and their rapid response to steroids. Radiol 97:521-.52h. 1970. I ? . Felson B: Less familiar roentgen patterns of pulmonary granulomas. AmerJ Roentgen 8:211-231, 1969. 14. Aach K and Kissane J: Wegener's granulomatosis. Amer J Med 48:496502. 1970. 15. Felson B and Braunstein H: Noninfectious necrotizing granulomatosix. Radiol 70:326-334. 1958. 16. Cassan SM, Coles DT and Harrison EG Jr.: The concept of limited forms of Wegener's granulomatosis. Amer J Med 49:366379. 1970. 17. Hulse R and Jung H: Wegener's granulomatosis in the region of paranasal sinuses and skull base. Roentgenological aspects. Fortshr Roentgen Str I15:561-572. 1971. 18. Smith S R , Smith JW and Theros EG: Wegener's granulomatosis, lymphomatoid variant. Radiol 98:439-444, 1971. 19. Calcaterra TC: Orolaryngeal histoplasmosis. Laryngscope 80: I I I- 170. 1970. 20. Kassel SH. Echevarria RA and Guzzo FD: Midline malignant reticulosis (so-called lethal midline granuloma). Cancer 23:920-935. 1969. 21. Zeek PM. Smith C C and Weeter J C : Studies on periarteritis nodosa I l l . The differentiation between the vascular lesions of periarteritis nodosa and hypersensitivity. Amer J Path 24:899-901, 1948. 2 2 . Leek PM: Periarteritis nodoh critical review. Amer J Clin Path 2 2 : 1952.
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