Vol. 115, May Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1976 by The Williams & Wilkins Co.
UROLOGIC MANIFESTATIONS OF POLYARTERITIS NODOSA AUSTINS. LITVAK, BRUCE A. LUCAS
AND
J. WILLIAM MCROBERTS
From the Division of Urology/Department of Surgery, University of Kentucky Medical Center, Lexington, Kentucky
ABSTRACT
Polyarteritis nodosa is an unusual condition that infrequently presents with signs and symptoms essentially confined to the urinary system. Such a case necessitating bilateral nephrectomy owing to hemorrhage is described. The pathologic findings, pathophysiology and etiology of the condition as well as treatment by renal transplantation are discussed. Polyarteritis nodosa is an unusual condition characterized by an absence of pathognomonic signs and symptoms but potentially involving all organ systems. The condition was first described in 1866 by Kussmaul and Maier' but it has been diagnosed only recently in early stages by means of angiography. 2 Urologists may have some superficial familiarity with the disease through testicular biopsies used for the diagnosis of 1 form of the disease. Since the disease does not present frequently with signs and symptoms essentially confined to the urinary system a case is described because of its unique approach to therapy. Additionally, the pathophysiology and treatment of this frequently fatal disease are discussed. CASE REPORT
R. N., a 20-year-old white man, was seen at another hospital with pain typical of a right ureteral calculus. Laboratory findings revealed a white blood count of 26,000, with a shift to the left. Urinalysis showed 50 red blood cells per high power field and a trace of albumin. The blood urea nitrogen (BUN) and creatinine were normal. An excretory urogram was suggestive of a right ureteral calculus with decreased function on the right side. Three days after hospitalization severe right flank and right upper quadrant pain developed and an exploratory laparotomy was done. There was marked right retroperitoneal hemorrhage, control of which could not be obtained and a right nephrectomy was performed. Postoperatively, the patient had persistent hematuria, proteinuria and an elevated white blood count. Cystoscopy and retrograde pyelography were done 9 days postoperatively and revealed extravasation from the patent right ureteral stump. After cystoscopy urinary output decreased and left lower quadrant pain, radiating into the left shoulder, developed 11 days postoperatively. The BUN was 70 mg. per cent, creatinine 3 mg. per cent and hematocrit 25 per cent. Urinary output was 21 cc per 24 hours. The patient was admitted to our hospital 13 days postoperatively. He had a BUN of 94 mg. per cent and creatinine of 8.6 mg. per cent. Physical examination revealed decreased breath sounds and dullness to percussion in the left hemithorax. The chest x-ray confirmed the presence of an infiltrate. There were left lower quadrant tenderness with a firm palpable mass in the left flank and ecchymoses above the left lower quadrant. The white blood count was 28,500 with a marked shift to the left, hematocrit 24.6 per cent and serum potassium 6.6 mg. per cent. A technetium pertechnetate perfusion scan showed minimal blood flow to the left kidney. Cystoscopy and left retrograde pyelograms revealed normal architecture of the left kidney. An arteriovenous shunt was placed and the patient underAccepted for publication September 5, 1975. 572
went dialysis and transfusion. After dialysis angiography revealed multiple aneurysms throughout the kidney as well as a large hepatic artery aneurysm (fig. 1). On the night of hospitalization the blood pressure decreased rapidly to shock levels and the patient was given another transfusion and taken to the operating room. An exploratory laparotomy was done, during which time the patient had a cardiac arrest and was resuscitated. Upon opening the abdomen a large left retroperitoneal hemorrhagic mass was seen. Exploration revealed that the kidney was ruptured and vascular control could not be secured so a left nephrectomy was done. Postoperatively, the patient was treated with dialysis and had an uneventfuI recover,y. Azathioprine and prednisone were started in an effort to pre~ent possible progression of this fulminant systemic disease process. Cerebral and coronary angiography did not reveal any other aneurysms and the hepatic aneurysm was resected with interposition of a dacron graft. Again the patient had an uneventful convalescence and was maintained on hemodialysis. Subsequently, a live related donor kidney transplant was done with early graft failure. Another transplantation 2 months later with a cadaver kidney provided almost 5 months of life-sustaining renal function until chronic rejection required reinstitution of hemodialysis. The patient is alive more than 1 year after the bilateral nephrectomy and is awaiting a third kidney transplant. He is being maintained on 25 mg. azathioprine daily and 20 mg. prednisone every other day without evidence of recurrent polyarteritis. He is doing well on chronic hemodialysis and has resumed his university studies. RADIOGRAPHIC CHARACTERISTICS OF POLYARTERITIS NODOSA
The radiographic diagnosis of polyarteritis nodosa has been extremely difficult. On a plain film the only finding often is a mass in the renal area. This mass may be characterized in 2 ways. When the hemorrhage is contained within the renal capsule or in the perirenal fat the mass is fairly well circumscribed and the psoas lines appear distinct. However, when the hemorrhage has ruptured beyond the limits of the capsule and is contained only by Gerota's fascia there is a hazy, indefinite mass obliterating the renal and psoas outline and often displacing the bowel. Radiographic non-function appears to be the usual finding and the retrograde pyelogram will appear normal. The recent use of renal angiography has been the outstanding contribution in the diagnosis of polyarteritis nodosa. Multiple small aneurysms in the medium-sized arteries, particularly at the bifurcations, would seem to be definitive findings in this disease. As may be seen from a selective angiogram these aneurysms are rather characteristic. It is on the basis of these x-ray findings that the diagnosis of polyarteritis nodosa can be made.
UROLOGIC MANIFESTATIONS OF POLYARTERITIS NODOSA
573
FIG. 1, A, selective renal angiogram demonstrates multiple aneurysms. B, flush aortogram reveals hepatic artery aneurysm
FIG. 2. A, sectioned specimen of left kidney reveals area of aneurysm (arrow). B, photomicrograph of left kidney specimen shows disruption of arterial wall with hemorrhage present.
574
LITVAK, LUCAS AND MCROBERTS PATHOLOGIC CHARACTERISTICS OF POLYARTERITIS NODOSA
Examination of the gross specimen revealed that there was marked hemorrhage throughout the kidney (fig. 2, A). This hemorrhage had dissected through the parenchyma and into the perirenal space. Microscopic examination of the kidney revealed the formation of multiple false aneurysms with disruption of the walls of the medium-sized arteries, particularly at the bifurcations (fig. 2, B). These aneurysms were diffusely present throughout the renal parenchyma and there was some evidence of infarction present. These findings in the kidney of the patient suffering with polyarteritis nodosa appear to be fairly typical. There is a massive or focal degeneration involving the arterial walls that may involve any or all coats in the acute phase. The necrosis involves the media and the lamina elastica, thereby weakening the wall, and hemorrhage and rupture occur along with thrombosis, infarction or aneurysmal formation. Microscopic examination may reveal a polymorphonuclear infiltrate with eosinophils about the area of necrosis and there may be an acute diffuse glomerulonephritis associated with the disease. 3 DISCUSSION
Generally, the prognosis of the condition has been poor. Treatment has been based on the use of chronic corticosteriod and azathioprine therapy. There have been case reports of regression of the lesion with the use of this modality. However, in the case presented no such treatment was possible initially. Bilateral nephrectomy was done because of the emergent condition of the patient and then azathioprine and prednisone were started postoperatively. This case is unique in its presentation and management and review of the American College of Surgeons/National Institute of Health Transplant Registry does not disclose any similar case coming to transplantation. SUMMARY AND CONCLUSIONS
Polyarteritis nodosa is an unusual disease that does not typically present as a urologic problem. A patient is described who underwent bilateral nephrectomy because of acute renal hemorrhage caused by aneurysmal rupture of intrarenal arteries. He has had 2 successive renal transplants with subsequent graft failures. He is now doing well on chronic hemodialysis awaiting his third transplant. The pathophysiology of polyarteritis nodosa is poorly understood but there appears to be a deposition of immune complexes in the walls of the medium and small arteries that progress, causing thrombosis and aneurysmal formation. This condition may be associated with a positive Australia antigenemia. Polyarteritis nodosa must be considered in the differential diagnosis of a patient with acute renal hemorrhage and radiographic non-function.
The pathophysiology of polyarteritis nodosa is poorly understood but there appears to be a deposition of immune complexes in the walls of medium and small arteries. These lesions progress causing degenerative changes in the arterial walls with thrombosis and aneurysmal formation. The reason for this deposition is unclear but may be similar to the findings produced in the experimental hypersensitivity model reported ADDENDUM by Rich and Gregory in 1943. • All forms of the disease are seen most often in patients between 20 and 60 years old, with men The patient underwent a third renal transplantation in Depredominating 3 to 1. cember 1975. The donor was his brother. Renal function is There appear to be several variants of the disease. In 1923 stable with a serum creatinine of 2.1 mg. Ophiils suggested a relationship between polyarteritis nodosa and rheumatic fever. 6 Friedberg and Gross reviewed 8 patients REFERENCES with polyarteritis nodosa and found that 4 ,;ases were associated with rheumatic fever and rheumatic heart disease.• In 1. Kussmaul, A. and Maier, R.: Ueber eine bisher nicht beschriebene eigenthumliche arlerienerkrankung (Periarteritis nodosa), die mit addition, there appear to be 2 variants as to location. In 1 Morbus Brightii und rapid fortschreitender allegmeiner muskell variant the findings of the disease seem to be limited to the soft ahmung einkergeht. Deutsch. Arch. Klin. Med., l: 484, 1866. tissue and peripheral vasculature, while in the other skin and 2. Bron, K. M., Strott, C. A. and Shapiro, A. P.: The diagnostic value muscle biopsies may not reveal evidence of disease, which is of angiographic observations in polyarteritis nodosa. A case of limited to the visceral organ systems. multiple aneurysms in the visceral organs. Arch. Intern. Med., ll6: 450, 1965. The disease has been related repeatedly to hypersensitivity 3. Leonhardt, E.T., Jakobson, H. and Ringqvist, 0. T.: Angiographic such as serum sickness and drug reactions. and clinicophysiologic investigation of a case of polyarteritis Some investigators have been impressed by the frequent nodosa. Amer. J. Med., 53: 242, 1972. association with respiratory infections. Recently, Mowrey and 4. Rich, A. R. and Gregory, J. E.: The experimental demonstration Lundberg emphasized the association between hepatitis or that periarteritis nodosa is a manifestation of hypersensitivity. cirrhosis and polyarteritis nodosa. 7 Trepo and associates noted Bull. Johns Hopkins Hosp., 72: 65, 1943. an association between the presence of Australia antigenemia 5. Ophuls, W.: Periarteritis acuta nodosa. Arch. Intern. Med., 32: 870, and polyarteritis nodosa. 8 While this association is not constant 1923. it appears often enough so the classification of polyarteritis 6. Friedberg, C. K. and Gross, L.: Periarteritis nodosa (necrotizing arteritis) associated with rheumatic heart disease, with a note on nodosa at this time must be considered not only on an abdominal rheumatism. Arch. Intern. Med., 54: 170, 1934. autoimmune basis but also on a viral basis. This division of etiology would be consistent with animal models in which a 7. Mowrey, F. H. and Lundberg, E. A.: The clinical manifestations of essential polyangiitis (periarteritis nodosa), with emphasis on similar vasculitis is present during chronic viral illnesses. 9 the hepatic manifestations. Ann. Intern. Med., 40: 1145, 1954. Those patients not having a positive finding for Australia 8. Trepo, C. G., Thivolet, J. and Prince, A. M.: Australia antigen and antigenemia may be considered a different group in which the polyarteritis nodosa. Amer. J. Dis. Child., 123: 390, 1972. immune complex results from circulating antigen excesses of 9. Leader, R. W., Wagner, B. M., Henson, J. B. and Gorham, J. R.: indeterminate origin. Indeed, polyarteritis nodosa may be a Structural and histochemical observations of liver and kidney in Aleutian disease of mink. Amer. J. Path., 43: 33, 1963. common pattern of vascular reaction to a variety of stimuli.
THE JOURNAL OF UROLOGY
Copyright© 1976 by The Williams & Wilkins Co.
UROLOGIC MANIFESTATIONS OF POLYARTERITIS NODOSA AUSTINS. LITVAK, BRUCE A. LUCAS
AND
J. WILLIAM MCROBERTS
From the Division of Urology/Department of Surgery, University of Kentucky Medical Center, Lexington, Kentucky
ABSTRACT
Polyarteritis nodosa is an unusual condition that infrequently presents with signs and symptoms essentially confined to the urinary system. Such a case necessitating bilateral nephrectomy owing to hemorrhage is described. The pathologic findings, pathophysiology and etiology of the condition as well as treatment by renal transplantation are discussed. Polyarteritis nodosa is an unusual condition characterized by an absence of pathognomonic signs and symptoms but potentially involving all organ systems. The condition was first described in 1866 by Kussmaul and Maier' but it has been diagnosed only recently in early stages by means of angiography. 2 Urologists may have some superficial familiarity with the disease through testicular biopsies used for the diagnosis of 1 form of the disease. Since the disease does not present frequently with signs and symptoms essentially confined to the urinary system a case is described because of its unique approach to therapy. Additionally, the pathophysiology and treatment of this frequently fatal disease are discussed. CASE REPORT
R. N., a 20-year-old white man, was seen at another hospital with pain typical of a right ureteral calculus. Laboratory findings revealed a white blood count of 26,000, with a shift to the left. Urinalysis showed 50 red blood cells per high power field and a trace of albumin. The blood urea nitrogen (BUN) and creatinine were normal. An excretory urogram was suggestive of a right ureteral calculus with decreased function on the right side. Three days after hospitalization severe right flank and right upper quadrant pain developed and an exploratory laparotomy was done. There was marked right retroperitoneal hemorrhage, control of which could not be obtained and a right nephrectomy was performed. Postoperatively, the patient had persistent hematuria, proteinuria and an elevated white blood count. Cystoscopy and retrograde pyelography were done 9 days postoperatively and revealed extravasation from the patent right ureteral stump. After cystoscopy urinary output decreased and left lower quadrant pain, radiating into the left shoulder, developed 11 days postoperatively. The BUN was 70 mg. per cent, creatinine 3 mg. per cent and hematocrit 25 per cent. Urinary output was 21 cc per 24 hours. The patient was admitted to our hospital 13 days postoperatively. He had a BUN of 94 mg. per cent and creatinine of 8.6 mg. per cent. Physical examination revealed decreased breath sounds and dullness to percussion in the left hemithorax. The chest x-ray confirmed the presence of an infiltrate. There were left lower quadrant tenderness with a firm palpable mass in the left flank and ecchymoses above the left lower quadrant. The white blood count was 28,500 with a marked shift to the left, hematocrit 24.6 per cent and serum potassium 6.6 mg. per cent. A technetium pertechnetate perfusion scan showed minimal blood flow to the left kidney. Cystoscopy and left retrograde pyelograms revealed normal architecture of the left kidney. An arteriovenous shunt was placed and the patient underAccepted for publication September 5, 1975. 572
went dialysis and transfusion. After dialysis angiography revealed multiple aneurysms throughout the kidney as well as a large hepatic artery aneurysm (fig. 1). On the night of hospitalization the blood pressure decreased rapidly to shock levels and the patient was given another transfusion and taken to the operating room. An exploratory laparotomy was done, during which time the patient had a cardiac arrest and was resuscitated. Upon opening the abdomen a large left retroperitoneal hemorrhagic mass was seen. Exploration revealed that the kidney was ruptured and vascular control could not be secured so a left nephrectomy was done. Postoperatively, the patient was treated with dialysis and had an uneventfuI recover,y. Azathioprine and prednisone were started in an effort to pre~ent possible progression of this fulminant systemic disease process. Cerebral and coronary angiography did not reveal any other aneurysms and the hepatic aneurysm was resected with interposition of a dacron graft. Again the patient had an uneventful convalescence and was maintained on hemodialysis. Subsequently, a live related donor kidney transplant was done with early graft failure. Another transplantation 2 months later with a cadaver kidney provided almost 5 months of life-sustaining renal function until chronic rejection required reinstitution of hemodialysis. The patient is alive more than 1 year after the bilateral nephrectomy and is awaiting a third kidney transplant. He is being maintained on 25 mg. azathioprine daily and 20 mg. prednisone every other day without evidence of recurrent polyarteritis. He is doing well on chronic hemodialysis and has resumed his university studies. RADIOGRAPHIC CHARACTERISTICS OF POLYARTERITIS NODOSA
The radiographic diagnosis of polyarteritis nodosa has been extremely difficult. On a plain film the only finding often is a mass in the renal area. This mass may be characterized in 2 ways. When the hemorrhage is contained within the renal capsule or in the perirenal fat the mass is fairly well circumscribed and the psoas lines appear distinct. However, when the hemorrhage has ruptured beyond the limits of the capsule and is contained only by Gerota's fascia there is a hazy, indefinite mass obliterating the renal and psoas outline and often displacing the bowel. Radiographic non-function appears to be the usual finding and the retrograde pyelogram will appear normal. The recent use of renal angiography has been the outstanding contribution in the diagnosis of polyarteritis nodosa. Multiple small aneurysms in the medium-sized arteries, particularly at the bifurcations, would seem to be definitive findings in this disease. As may be seen from a selective angiogram these aneurysms are rather characteristic. It is on the basis of these x-ray findings that the diagnosis of polyarteritis nodosa can be made.
UROLOGIC MANIFESTATIONS OF POLYARTERITIS NODOSA
573
FIG. 1, A, selective renal angiogram demonstrates multiple aneurysms. B, flush aortogram reveals hepatic artery aneurysm
FIG. 2. A, sectioned specimen of left kidney reveals area of aneurysm (arrow). B, photomicrograph of left kidney specimen shows disruption of arterial wall with hemorrhage present.
574
LITVAK, LUCAS AND MCROBERTS PATHOLOGIC CHARACTERISTICS OF POLYARTERITIS NODOSA
Examination of the gross specimen revealed that there was marked hemorrhage throughout the kidney (fig. 2, A). This hemorrhage had dissected through the parenchyma and into the perirenal space. Microscopic examination of the kidney revealed the formation of multiple false aneurysms with disruption of the walls of the medium-sized arteries, particularly at the bifurcations (fig. 2, B). These aneurysms were diffusely present throughout the renal parenchyma and there was some evidence of infarction present. These findings in the kidney of the patient suffering with polyarteritis nodosa appear to be fairly typical. There is a massive or focal degeneration involving the arterial walls that may involve any or all coats in the acute phase. The necrosis involves the media and the lamina elastica, thereby weakening the wall, and hemorrhage and rupture occur along with thrombosis, infarction or aneurysmal formation. Microscopic examination may reveal a polymorphonuclear infiltrate with eosinophils about the area of necrosis and there may be an acute diffuse glomerulonephritis associated with the disease. 3 DISCUSSION
Generally, the prognosis of the condition has been poor. Treatment has been based on the use of chronic corticosteriod and azathioprine therapy. There have been case reports of regression of the lesion with the use of this modality. However, in the case presented no such treatment was possible initially. Bilateral nephrectomy was done because of the emergent condition of the patient and then azathioprine and prednisone were started postoperatively. This case is unique in its presentation and management and review of the American College of Surgeons/National Institute of Health Transplant Registry does not disclose any similar case coming to transplantation. SUMMARY AND CONCLUSIONS
Polyarteritis nodosa is an unusual disease that does not typically present as a urologic problem. A patient is described who underwent bilateral nephrectomy because of acute renal hemorrhage caused by aneurysmal rupture of intrarenal arteries. He has had 2 successive renal transplants with subsequent graft failures. He is now doing well on chronic hemodialysis awaiting his third transplant. The pathophysiology of polyarteritis nodosa is poorly understood but there appears to be a deposition of immune complexes in the walls of the medium and small arteries that progress, causing thrombosis and aneurysmal formation. This condition may be associated with a positive Australia antigenemia. Polyarteritis nodosa must be considered in the differential diagnosis of a patient with acute renal hemorrhage and radiographic non-function.
The pathophysiology of polyarteritis nodosa is poorly understood but there appears to be a deposition of immune complexes in the walls of medium and small arteries. These lesions progress causing degenerative changes in the arterial walls with thrombosis and aneurysmal formation. The reason for this deposition is unclear but may be similar to the findings produced in the experimental hypersensitivity model reported ADDENDUM by Rich and Gregory in 1943. • All forms of the disease are seen most often in patients between 20 and 60 years old, with men The patient underwent a third renal transplantation in Depredominating 3 to 1. cember 1975. The donor was his brother. Renal function is There appear to be several variants of the disease. In 1923 stable with a serum creatinine of 2.1 mg. Ophiils suggested a relationship between polyarteritis nodosa and rheumatic fever. 6 Friedberg and Gross reviewed 8 patients REFERENCES with polyarteritis nodosa and found that 4 ,;ases were associated with rheumatic fever and rheumatic heart disease.• In 1. Kussmaul, A. and Maier, R.: Ueber eine bisher nicht beschriebene eigenthumliche arlerienerkrankung (Periarteritis nodosa), die mit addition, there appear to be 2 variants as to location. In 1 Morbus Brightii und rapid fortschreitender allegmeiner muskell variant the findings of the disease seem to be limited to the soft ahmung einkergeht. Deutsch. Arch. Klin. Med., l: 484, 1866. tissue and peripheral vasculature, while in the other skin and 2. Bron, K. M., Strott, C. A. and Shapiro, A. P.: The diagnostic value muscle biopsies may not reveal evidence of disease, which is of angiographic observations in polyarteritis nodosa. A case of limited to the visceral organ systems. multiple aneurysms in the visceral organs. Arch. Intern. Med., ll6: 450, 1965. The disease has been related repeatedly to hypersensitivity 3. Leonhardt, E.T., Jakobson, H. and Ringqvist, 0. T.: Angiographic such as serum sickness and drug reactions. and clinicophysiologic investigation of a case of polyarteritis Some investigators have been impressed by the frequent nodosa. Amer. J. Med., 53: 242, 1972. association with respiratory infections. Recently, Mowrey and 4. Rich, A. R. and Gregory, J. E.: The experimental demonstration Lundberg emphasized the association between hepatitis or that periarteritis nodosa is a manifestation of hypersensitivity. cirrhosis and polyarteritis nodosa. 7 Trepo and associates noted Bull. Johns Hopkins Hosp., 72: 65, 1943. an association between the presence of Australia antigenemia 5. Ophuls, W.: Periarteritis acuta nodosa. Arch. Intern. Med., 32: 870, and polyarteritis nodosa. 8 While this association is not constant 1923. it appears often enough so the classification of polyarteritis 6. Friedberg, C. K. and Gross, L.: Periarteritis nodosa (necrotizing arteritis) associated with rheumatic heart disease, with a note on nodosa at this time must be considered not only on an abdominal rheumatism. Arch. Intern. Med., 54: 170, 1934. autoimmune basis but also on a viral basis. This division of etiology would be consistent with animal models in which a 7. Mowrey, F. H. and Lundberg, E. A.: The clinical manifestations of essential polyangiitis (periarteritis nodosa), with emphasis on similar vasculitis is present during chronic viral illnesses. 9 the hepatic manifestations. Ann. Intern. Med., 40: 1145, 1954. Those patients not having a positive finding for Australia 8. Trepo, C. G., Thivolet, J. and Prince, A. M.: Australia antigen and antigenemia may be considered a different group in which the polyarteritis nodosa. Amer. J. Dis. Child., 123: 390, 1972. immune complex results from circulating antigen excesses of 9. Leader, R. W., Wagner, B. M., Henson, J. B. and Gorham, J. R.: indeterminate origin. Indeed, polyarteritis nodosa may be a Structural and histochemical observations of liver and kidney in Aleutian disease of mink. Amer. J. Path., 43: 33, 1963. common pattern of vascular reaction to a variety of stimuli.
