- Email: [email protected]
Bilateral Ureteral Obstruction Following Sulfamethoxazole
Vol. 98, Oct. Printed in U.S.A
THE JOURNAL OF UROLOGY
Copyright © 1967 by The Williams & Wilkins Co.
BILATERAL URETERAL OBSTRUCTION FOLLOWING SULFAMETHOXAZOLE LEWIS I. SCHAINUCK
AND
JESSIE E. HANO
From the Department of Metabolism, Walter Reed Army Institute of Research, Washington, D. C.
Sulfonamide derivatives have been implicated in the development of a variety of hypersensitivity reactions. 1 • 2 The following report describes a case in which bilateral ureteral obstruction developed acutely following administration of sulfamethoxazole and regressed spontaneously after cessation of the drug. We believe that this is the first published account of such a relationship. CASE REPORT
A 67-year-old white man was transferred to the renal service of Walter Reed General Hospital because of anuria, 3 days in duration. Six days before his admission, he was given sulfamethoxazole (gantanol) 1.0 gm. 4 times daily for a lower urinary tract infection. Two days later, he suffered pruritic swelling of his hands and feet, abdominal rash, followed by anorexia, vomiting and diffuse abdominal pain which radiated to both flanks, back and testes. The gantanol was discontinued but despite this, distention, obstipation and anuria developed. Three days before this admission he entered another hospital where a plain film of the kidney, ureter and bladder (KUB) showed dilated loops of bowel and a barium enema demonstrated diverticula without obstruction; while there he had a temperature of 104F and delirium. He was given penicillin and streptomycin and an indwelling catheter was placed in his bladder. Because of persistent anuria he was transferred to our hospital with a diagnosis of acute renal failure. The patient had had symptoms of prostatism for about 6 months and had consulted a physician 2 months previously. At that time, his prostate was described as enlarged, the blood urea nitrogen (BUN) was 15 mg. per 100 cc and an excretory urogram was normal (fig. 1, A). No medications were given. Review of his past medical history
Accepted for publication November 1, 1966. Weinstein, L., JV[adoff, M. A. and Samet, C. M.: The sulfonamides. New Engl. J. Med., 263: 952-957, 1960. 2 Lehr, D.: Clinical toxicity of sulfonamides. Ann. New York Acad. Sci., 69: 417-447, 1957. 1
revealed chronic bronchitis and sinusitis for about 20 years; otherwise, the patient had been in excellent health. There was no history of hay fever, rash, drug allergy or migraine. He had taken penicillin but had never reacted adversely to it and for the past 6 months had been taking co-pyronil for his sinusitis. Careful drug history revealed no other medication in the past 2 years. Physical examination revealed a confused, obese, elderly man in mild respiratory distress. His blood pressure was 140/110; pulse, 140; temperature, 98.4F and respiration 22. Ophthalmoscopic examination showed mild arteriovenous nicking. The neck veins were slightly distended. The anteroposterior diameter of the chest was increased, there was poor respiratory excursion and auscultation demonstrated bibasilar rales. Cardiac sounds were poorly heard. The abdomen was distended, tympanitic and diffusely tender to palpation and there was marked bilateral costovertebral angle tenderness. However, peristaltic sounds were normal and no mass was palpated. Rectal examination disclosed an enlarged prostate. There was no edema, rash or neurologic abnormality. The BUN was 90 mg. per 100 cc; serum sodium, 127 meq. per liter; potassium, 5.7 meq. per liter; chloride, 94 meq. per liter and carbon dioxide, 14.5 meq. per liter. Thehematocrit was 45 per cent and the white blood count was 20,000 per cu. mm. with 70 per cent segmented neutrophils and 18 per cent lymphocytes. Urinalysis demonstrated 2 plus protein, numerous red and white blood cells and no sulfa crystals. Urine and blood cultures were sterile. A chest film showed borderline cardiomegaly and a bilateral infiltrate consistent with pulmonary congestion. A KUB showed dilated large bowel and barium in the cecum. Digitalis was given for signs of congestive failure and, because of the possibility of sepsis, penicillin and chloramphenicol were administered. The following day a left retrograde pyelogram was performed. A ureteral obstruction was found at the 3rd to 4th lumbar vertebrae with hydrometer and hydronephrosis above that point and
466
BILATERAL URETERAL OBS'l'RUCTION FOLLOWING SULFAMETHOXAZOLE
467
Fm. 1. A, excretory urogram 6 weeks prior to hospitalization. B, left retrograde pyelogram sbows angulation and medial deviation of ureter. C, constant infnsion excretory nrogram on 7th day of illness demonstrates bilateral fnuctiou with hydro ureter and hydrouephrosis. D, excretory urogrmn 4 month8 after acute illness.
marked angulation of the ureter (fig. I, B). The urine obtained from the JJelvis was clear, contained no crystals and was sterile. A ureteral catheter was retained iu the left ureter and an indwelling catheter wa3 left in the bladder. During the next 36 hours diuresis ensued amounting to 7.0 liters. Initiall~- uriue flowed from the ureteral catheter only but shortly thereafter both catheters produced approximately equal volumes indicating Bpontaneous diuresis from the right ureter. The DUN decreased from 112 to 24 mg. per 100 cc and creatiui11e decreased from 15.6 to 1.6 mg. per 100 cc (fig. 2). The patient ,rns scheduled for bilateral nephrostomies 3 days after hmpitalization; hmv-
ever, prior to this procedure, the ureteral catheter was removed and an excretory urogram ,va~ per· formed (fig. 1, C). Dye appeared in both kidneys and ureters and bilateral hydroureter and nephrosis with medial deviation of the ureters was demonstrated. The operative procedure ,n;.q canceled and a catheter was left in place because of bladder neck obstruction from the prostate. The patient c:cmtiuued to excrete normal amounts of urine and t.he creatinine clearance, 6 days after admission, was 81 ml. per minute. ~.\.bdorninal pain and distention peared and the patient was asymptomatic except for chronic en:1physema and rn.ild conge~tive beart failure which were well compensated
468
SCHAINUCK AND HANO
mgm"/o Left Ureteral
Days from Onset
Fm. 2. Diuresis following left ureteral catheterization digitalis and bronchial dilators. One month after admission he underwent prostatectomy. An excretory urogram 4 months later was normal (fig. 1, D). COMMENT
Sulfonamide derivatives can produce a wide variety of hyperergic reactions including bone marrow suppression, hemolytic anern.ia, vasculitis, serum sickness, erythema nodosum and Stevens-Johnson syndrome. 1 • 2 Rash, edema and fever, followed by the rapid development of bilateral ureteral obstruction, coincident with the administration of the sulfonamide, and their spontaneous regression following cessation of therapy suggest that the drug was the etiologic factor. Although intrarenal obstruction from sulfonamide crystallization with subsequent spontaneous diuresis cannot be completely excluded, the absence of sulfa crystals in both bladder and pelvic urine specimens makes this unlikely. Acute overwhelming pyelonephritis with ureteritis conceivably could have produced the sequence described, but no evidence of such a process could be demonstrated in either pelvic or bladder urine specimen. The demonstration of bilateral ureteral obstruction together with angulation and medial deviation of the ureters suggested the presence of an acute retroperitoneal inflammatory process. The clinical and radiologic features of idiopathic retroperitoneal fibrosis have been extensively described3 • 4 and the findings in this disease bear Ormond, J. K.: Idiopathic retroperitoneal fibrosis: An established clinical entity. J.A.M.A., 3
174: 1561-1568, 1960. 4 Brown, K. A., Staubitz, W. J., Oberkircher, 0. J. and Niesen, W. C.: A review of retroperitoneal fibrosis. J. Urol., 92: 323-330, 1964.
a striking resemblance to the case herein reported. The disease usually develops in an insidious manner with nausea, fever, abdominal and back pain and then progresses to ureteral obstruction and uremia. However, it can develop acutely as evidenced by a recent report of 2 patients who presented the features of an acute abdorn.en. At exploration, the characteristic pathologic features of retroperitoneal fibrosis were found. 5 The inflammatory process can affect various organs and many features suggest the presence of a hypersensitivity state or collagen vascular disease. 5- 9 Two recent publications have clearly implicated methisergide as an etiologic factor in the development of this syndrome 10 , 11 and it is possible that other pharmacologic agents may behave similarly. Although no biopsy was performed and our patient was not explored, the clinical and radiologic presentations are suggestive of an early reversible stage of retroperitoneal fibrosis which was drug induced. 5 Thompson, R. J., Jr., Carter, R., Gibson, L. D., Reiswig, 0. K. and Hinshaw, D. B.: Acute idiopathic retroperitoneal fibrosis. Ann. Surg., 153:
399-406, 1961. 6 Que, G. S. and Mandema, E.: A case of idiopathic retroperitoneal fibrosis presenting as a systemic collagen disease. Amer. J . .Med., 36: 320-
329, 1964. 7 Kay, R. G.: Retroperitoneal vasculitis with perivascular fibrosis. Brit. J. Urol., 35: 284-291,
1963. 8 Hoffman, W. W. and Trippel, 0. H.: Retroperitoneal fibrosis: Etiologic considerations. J. Urol., 86: 222-231, 1961. 9 Ormond, J. K.: Idiopathic retroperitoneal fibrosis: A discussion of the etiology. J. Urol., 9i:
38.5-390, 196.5. 10 Graham, J. R., Suby, H. I., LeCompte, P. R. and Sadowsky, N. L.: Fibrotic disorders associated with methysergide therapy for headache. New Engl. J. Med., 274: 359-368, 1966. 11 Suby, H. I., Kerr, W. S., Jr., Graham, J. R. and Fraley, E.: Retroperitoneal fibrosis: A missing link in the chain. J. Urol., 93: 144-152, 1965.
BILATERAL UHETERAL OBSTRUCTIO;\; FOLLOWING SULFAMETHOXAZOLE
\Ve did not feel justified in rechallenging the patient with sulfamcthoxazole and, therefore, the etiologic role of the agent in producing the syndrome described cannot he proved. However, ;cute bilateral obstruction should be considered in any patient presenting with acute renal failure if obstruction is demonstrated, drug hypershould be excluded by withdrawal of all medication,5 before an operation is attempted.
4()D
SU:VIMARY
A case of bilateral ureteral obstruction with medial deviation of the ureters administration of sulfamethoxazole is The illness resembled a hypersensitivity reaction and the obstrnction resolved spontaneou,ly aftei cessation of the drug. It is postulated that the entire syndrome was a hyperergic reaction to th:: sulfonamide.
THE JOURNAL OF UROLOGY
Copyright © 1967 by The Williams & Wilkins Co.
BILATERAL URETERAL OBSTRUCTION FOLLOWING SULFAMETHOXAZOLE LEWIS I. SCHAINUCK
AND
JESSIE E. HANO
From the Department of Metabolism, Walter Reed Army Institute of Research, Washington, D. C.
Sulfonamide derivatives have been implicated in the development of a variety of hypersensitivity reactions. 1 • 2 The following report describes a case in which bilateral ureteral obstruction developed acutely following administration of sulfamethoxazole and regressed spontaneously after cessation of the drug. We believe that this is the first published account of such a relationship. CASE REPORT
A 67-year-old white man was transferred to the renal service of Walter Reed General Hospital because of anuria, 3 days in duration. Six days before his admission, he was given sulfamethoxazole (gantanol) 1.0 gm. 4 times daily for a lower urinary tract infection. Two days later, he suffered pruritic swelling of his hands and feet, abdominal rash, followed by anorexia, vomiting and diffuse abdominal pain which radiated to both flanks, back and testes. The gantanol was discontinued but despite this, distention, obstipation and anuria developed. Three days before this admission he entered another hospital where a plain film of the kidney, ureter and bladder (KUB) showed dilated loops of bowel and a barium enema demonstrated diverticula without obstruction; while there he had a temperature of 104F and delirium. He was given penicillin and streptomycin and an indwelling catheter was placed in his bladder. Because of persistent anuria he was transferred to our hospital with a diagnosis of acute renal failure. The patient had had symptoms of prostatism for about 6 months and had consulted a physician 2 months previously. At that time, his prostate was described as enlarged, the blood urea nitrogen (BUN) was 15 mg. per 100 cc and an excretory urogram was normal (fig. 1, A). No medications were given. Review of his past medical history
Accepted for publication November 1, 1966. Weinstein, L., JV[adoff, M. A. and Samet, C. M.: The sulfonamides. New Engl. J. Med., 263: 952-957, 1960. 2 Lehr, D.: Clinical toxicity of sulfonamides. Ann. New York Acad. Sci., 69: 417-447, 1957. 1
revealed chronic bronchitis and sinusitis for about 20 years; otherwise, the patient had been in excellent health. There was no history of hay fever, rash, drug allergy or migraine. He had taken penicillin but had never reacted adversely to it and for the past 6 months had been taking co-pyronil for his sinusitis. Careful drug history revealed no other medication in the past 2 years. Physical examination revealed a confused, obese, elderly man in mild respiratory distress. His blood pressure was 140/110; pulse, 140; temperature, 98.4F and respiration 22. Ophthalmoscopic examination showed mild arteriovenous nicking. The neck veins were slightly distended. The anteroposterior diameter of the chest was increased, there was poor respiratory excursion and auscultation demonstrated bibasilar rales. Cardiac sounds were poorly heard. The abdomen was distended, tympanitic and diffusely tender to palpation and there was marked bilateral costovertebral angle tenderness. However, peristaltic sounds were normal and no mass was palpated. Rectal examination disclosed an enlarged prostate. There was no edema, rash or neurologic abnormality. The BUN was 90 mg. per 100 cc; serum sodium, 127 meq. per liter; potassium, 5.7 meq. per liter; chloride, 94 meq. per liter and carbon dioxide, 14.5 meq. per liter. Thehematocrit was 45 per cent and the white blood count was 20,000 per cu. mm. with 70 per cent segmented neutrophils and 18 per cent lymphocytes. Urinalysis demonstrated 2 plus protein, numerous red and white blood cells and no sulfa crystals. Urine and blood cultures were sterile. A chest film showed borderline cardiomegaly and a bilateral infiltrate consistent with pulmonary congestion. A KUB showed dilated large bowel and barium in the cecum. Digitalis was given for signs of congestive failure and, because of the possibility of sepsis, penicillin and chloramphenicol were administered. The following day a left retrograde pyelogram was performed. A ureteral obstruction was found at the 3rd to 4th lumbar vertebrae with hydrometer and hydronephrosis above that point and
466
BILATERAL URETERAL OBS'l'RUCTION FOLLOWING SULFAMETHOXAZOLE
467
Fm. 1. A, excretory urogram 6 weeks prior to hospitalization. B, left retrograde pyelogram sbows angulation and medial deviation of ureter. C, constant infnsion excretory nrogram on 7th day of illness demonstrates bilateral fnuctiou with hydro ureter and hydrouephrosis. D, excretory urogrmn 4 month8 after acute illness.
marked angulation of the ureter (fig. I, B). The urine obtained from the JJelvis was clear, contained no crystals and was sterile. A ureteral catheter was retained iu the left ureter and an indwelling catheter wa3 left in the bladder. During the next 36 hours diuresis ensued amounting to 7.0 liters. Initiall~- uriue flowed from the ureteral catheter only but shortly thereafter both catheters produced approximately equal volumes indicating Bpontaneous diuresis from the right ureter. The DUN decreased from 112 to 24 mg. per 100 cc and creatiui11e decreased from 15.6 to 1.6 mg. per 100 cc (fig. 2). The patient ,rns scheduled for bilateral nephrostomies 3 days after hmpitalization; hmv-
ever, prior to this procedure, the ureteral catheter was removed and an excretory urogram ,va~ per· formed (fig. 1, C). Dye appeared in both kidneys and ureters and bilateral hydroureter and nephrosis with medial deviation of the ureters was demonstrated. The operative procedure ,n;.q canceled and a catheter was left in place because of bladder neck obstruction from the prostate. The patient c:cmtiuued to excrete normal amounts of urine and t.he creatinine clearance, 6 days after admission, was 81 ml. per minute. ~.\.bdorninal pain and distention peared and the patient was asymptomatic except for chronic en:1physema and rn.ild conge~tive beart failure which were well compensated
468
SCHAINUCK AND HANO
mgm"/o Left Ureteral
Days from Onset
Fm. 2. Diuresis following left ureteral catheterization digitalis and bronchial dilators. One month after admission he underwent prostatectomy. An excretory urogram 4 months later was normal (fig. 1, D). COMMENT
Sulfonamide derivatives can produce a wide variety of hyperergic reactions including bone marrow suppression, hemolytic anern.ia, vasculitis, serum sickness, erythema nodosum and Stevens-Johnson syndrome. 1 • 2 Rash, edema and fever, followed by the rapid development of bilateral ureteral obstruction, coincident with the administration of the sulfonamide, and their spontaneous regression following cessation of therapy suggest that the drug was the etiologic factor. Although intrarenal obstruction from sulfonamide crystallization with subsequent spontaneous diuresis cannot be completely excluded, the absence of sulfa crystals in both bladder and pelvic urine specimens makes this unlikely. Acute overwhelming pyelonephritis with ureteritis conceivably could have produced the sequence described, but no evidence of such a process could be demonstrated in either pelvic or bladder urine specimen. The demonstration of bilateral ureteral obstruction together with angulation and medial deviation of the ureters suggested the presence of an acute retroperitoneal inflammatory process. The clinical and radiologic features of idiopathic retroperitoneal fibrosis have been extensively described3 • 4 and the findings in this disease bear Ormond, J. K.: Idiopathic retroperitoneal fibrosis: An established clinical entity. J.A.M.A., 3
174: 1561-1568, 1960. 4 Brown, K. A., Staubitz, W. J., Oberkircher, 0. J. and Niesen, W. C.: A review of retroperitoneal fibrosis. J. Urol., 92: 323-330, 1964.
a striking resemblance to the case herein reported. The disease usually develops in an insidious manner with nausea, fever, abdominal and back pain and then progresses to ureteral obstruction and uremia. However, it can develop acutely as evidenced by a recent report of 2 patients who presented the features of an acute abdorn.en. At exploration, the characteristic pathologic features of retroperitoneal fibrosis were found. 5 The inflammatory process can affect various organs and many features suggest the presence of a hypersensitivity state or collagen vascular disease. 5- 9 Two recent publications have clearly implicated methisergide as an etiologic factor in the development of this syndrome 10 , 11 and it is possible that other pharmacologic agents may behave similarly. Although no biopsy was performed and our patient was not explored, the clinical and radiologic presentations are suggestive of an early reversible stage of retroperitoneal fibrosis which was drug induced. 5 Thompson, R. J., Jr., Carter, R., Gibson, L. D., Reiswig, 0. K. and Hinshaw, D. B.: Acute idiopathic retroperitoneal fibrosis. Ann. Surg., 153:
399-406, 1961. 6 Que, G. S. and Mandema, E.: A case of idiopathic retroperitoneal fibrosis presenting as a systemic collagen disease. Amer. J . .Med., 36: 320-
329, 1964. 7 Kay, R. G.: Retroperitoneal vasculitis with perivascular fibrosis. Brit. J. Urol., 35: 284-291,
1963. 8 Hoffman, W. W. and Trippel, 0. H.: Retroperitoneal fibrosis: Etiologic considerations. J. Urol., 86: 222-231, 1961. 9 Ormond, J. K.: Idiopathic retroperitoneal fibrosis: A discussion of the etiology. J. Urol., 9i:
38.5-390, 196.5. 10 Graham, J. R., Suby, H. I., LeCompte, P. R. and Sadowsky, N. L.: Fibrotic disorders associated with methysergide therapy for headache. New Engl. J. Med., 274: 359-368, 1966. 11 Suby, H. I., Kerr, W. S., Jr., Graham, J. R. and Fraley, E.: Retroperitoneal fibrosis: A missing link in the chain. J. Urol., 93: 144-152, 1965.
BILATERAL UHETERAL OBSTRUCTIO;\; FOLLOWING SULFAMETHOXAZOLE
\Ve did not feel justified in rechallenging the patient with sulfamcthoxazole and, therefore, the etiologic role of the agent in producing the syndrome described cannot he proved. However, ;cute bilateral obstruction should be considered in any patient presenting with acute renal failure if obstruction is demonstrated, drug hypershould be excluded by withdrawal of all medication,5 before an operation is attempted.
4()D
SU:VIMARY
A case of bilateral ureteral obstruction with medial deviation of the ureters administration of sulfamethoxazole is The illness resembled a hypersensitivity reaction and the obstrnction resolved spontaneou,ly aftei cessation of the drug. It is postulated that the entire syndrome was a hyperergic reaction to th:: sulfonamide.