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Ureteritis Cystica: Treatment with Sulfadiazine, Penicillin and Aureomycin Report of a Case
THE JOURNAL OF UROLOGY
Vol. 68, No. 5, November 1952 Printed in U.S.A.
URETERITIS CYSTICA: TREATMENT WITH SULFADIAZINE, PENICILLIN AND AUREOMYCIN REPORT OF A CASE B.G. CLARKE From the Departments of Urology, New Haven Hospital and Yale University School of Medicine, New Haven, Conn.
A case of ureteritis cystica in which the lesions disappeared and a sustained remission was produced by treatment with antibiotics has been studied. Our purpose in reporting this case is, first, to offer an observation relevant to the long discussed question of the pathogenesis of this condition; and second, to record a satisfactory therapeutic response. The literature contains only a few reports of successful treatment of this disease and none which we can discover by antibiotics. Morgagni, in 1761, described ureteritis cystica for the first time and noted its association with urinary tract inflammation. He observed "hydatids" within the ureters of two old men who had died with urinary tract inflammation associated in one case with what today would have been recognized as prostatism and in the other with posterior urethral stricture. In 1887 von Limbeck's microscopic studies showed that these lesions are multiple, small, subepithelial cysts, lined with cuboidal or transitional epithelium and anatomically indistinguishable from the structures found in cystitis cystica. In the same material he found downward sprouts of epithelium which he postulated assumed cystic form. Von Brunn, 6 years later, gave the name of cell nests to these epithelial sprouts as they appeared when separated from the parent epithelial layer. Herxheimer, reviewing his own material and the collected observations of others in 1906, recognized epithelial sprouts, cell nests, and the cysts as progressive phases of a proliferative response of urinary tract epithelium to chronic inflammation. Giani, in the same year, reported having reproduced the lesions of cystitis cystica experimentally by inducing chronic inflammation within the bladders of rabbits. Utilizing cystoscopic observations, Hinman, Johnson and McCorkle recognized the association of cystitis cystica with inflammatory conditions of the urinary tract. Warrick successfully demonstrated bacterial infection in twenty of twenty-eight cases of the same disease, with E. coli as the commonest organism. The development of urography has made recognition of ureteropyelitis cystica possible in the living patient. Little however is known of the natural history of the disease and from the few published reports available it is difficult to construct a characteristic clinical picture because the symptoms do not differ specifically from those of other inflammatory or obstructive lesions of the urinary tract. The writer acknowledges his gratitude to Dr. Clyde L. Deming, Professor of Urology in the Yale University School of Medicine for aid in preparation of the report; to Dr. Arnold H. Janzen, Professor of Radiology for critical scrutiny of the radiographic evidence; and to Dr. Michael S. Hovenanian, former Instructor in Urology for guidance in management of the case,
815
816
B. G. CLARKE
It is of interest that in 1934 Hinman and his associates concluded that "the first step in the treatment of the condition is obviously the removal of the source or cause of the inflammatory process." Five years later, Burkland and Leadbetter produced symptomatic improvement in a case of pyelo-ureteritis and cystitis cystica with pure cultures of H. influenzae by treatment with sulfanilamide but could not eradicate the organism permanently from the urine. Toulson reported having treated 2 patients with ureteritis cystica with sulfaniazine without effect. Kindall had brought about disappearance of the lesions in one case by placement of large ureteral catheters for 3 days followed by injection of silver nitrate. Kopp treated a case in similar manner with success. There are a number of reported instances of resection of the involved portion of the upper urinary tract for ureteropyelitis cystica. Our patient was a man in whom obstruction of the calyces of the right kidney had been produced by a process identified by excretory and retrograde pyelography as typical pyelo-ureteritis cystica. The history was consistent with the presence of chronic lower urinary tract infection. Because he had been given penicillin a half day before he came under our care, bacteriologic identification of the upper urinary tract invader was impossible and a combination of drugs was used. Within 2 days he was free of fever and pain, and within 9 days urograms showed that his upper urinary tract had returned to normal. He remained well during a year of observation, at the end of which his urograms were normal and his urine uninfected. CASE REPORT
A 29 year old man (L. G., 035611) was admitted to New Haven Hospital on July 30, 1950, because of constant right lower abdominal pain radiating to the right testis accompanied by vomiting. He had had gonorrhea 10 years before admission and 2 weeks before being referred to us a second attack of the same disease had been treated with penicillin with prompt relief. Three days before he came to the hospital, burning micturition and a slight urethral discharge had recurred. A short time after the onset of his pain on the day of admission he had been seen by a physician who had found gonococci in a smear of the prostatic secretion and administered an injection of penicillin. Because of persistent pain and vomiting he came to the hospital 6 hours later. At the time of admission he was uncomfortable and flushed. Temperature was 99.4 orally, pulse 90 and blood pressure 136/102. Abnormal physical findings were otherwise limited to deep tenderness in the right hypogastrium. His red blood cell count was 6.0 million, hemoglobin 16.0 gm., white blood cell count 14,000 with 85 per cent polymorphonuclear forms, 12 per cent lymphocytes, 2 per cent monocytes and 1 per cent eosinophils. The urine was of amber, smoky appearance, with a pH of 8.0, and contained no albumin or sugar. One hundred red blood cells and 5 white blood cells were seen in the high power field of the centrifuged sediment although no organisms were noted in the stained smear or subsequently reported in cultures. The blood nonprotein nitrogen and an x-ray of the abdomen were normal.
URETERITIS CYSTICA
817
The findings presented by this patient were regarded as consistent with either acute pyelonephritis with or without ureteral obstruction, or acute appendicitis, and consultants agreed upon overnight observation. Seventeen hours after the pain had begun, an excretory urogram showed a normal left upper urinary tract, but tubular diodrast excretion on the right side blocked within the pelvis (fig. 1, A). Cystoscopy revealed an easily dilated posterior urethral stricture, moderate trigonal hypertrophy, and a right ureteral meatus which was not seen to excrete urine. The ureteral catheter (No. 5F) was introduced on the right side with difficulty. Fluid irrigated from the right pelvis contained no organisms in smear or culture, and the left kidney urine was sterile. Phenolsulfonphthalein excretion
FrG. 1. A, excretory urogram 1 hour after injection of diodrast. Dye appears within kidney but does not fill pelvis or ureter. B, retrograde pyelogram. Small spherical filling defects throughout right ureter and a similar process deforming shadow of right pelvis. C, retrograde pyelogram after 14 days of treatment. Right upper urinary tract is now normal. Pressure of injection resulted in some pyelotubular reflux.
from the right kidney was nil; from the left the dye appeared in 3 minutes with secretion of 20 per cent in 15 minutes. The pyelo-ureterogram on the right showed many small spherical filling defects in the ureter with obstruction at the calyces by a similar process (fig. 1, B). The left pyelo-ureterogram was normal. For the next 14 days treatment consisted of daily doses of 2 0 gm. of sulfadiazine and 1.0 gm. of aureomycin orally, and 600,000 units of procaine penicillin intramuscularly. In 36 hours the patient was free of abdominal pain and in 48 his fever had subsided. On the ninth day an excretory urogram showed normal dye excretion on both sides with disappearance of pyelo-ureteritis cystica. Retrograde examination on the fourteenth day showed normal pyelo-ureteral
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B. G. CLARKE
shadows (fig. 1, C), no infection in either kidney, and normal phthalein excretion from both kidneys. At the end of a year, during which he had remained well, the patient permitted examination by excretory urography which was normal. The urine remained sterile. SUMMARY
A case is reported in which renal obstruction was produced by pyelo-ureteritis cystica on the right side. Under treatment with sulfadiazine, aureomycin and penicillin there was prompt relief of obstruction and disappearance of the lesions. After a year the upper urinary tracts remained normal. Evidence in this case corroborates the inflammatory pathogenesis of pyeloureteritis cystica and suggests that further trials of antibiotics may be warranted in this condition.
943 Oak St., Winnetka, Ill. REFERENCES BoTHE, A. E., AND CmsToL, D.S.: Am. J. Roentgenol., 48: 787-793, 1942. VON BRUNN, A.: Arch. f. mik. Anat., 41: 294-302, 1893. BURKLAND, C. E. AND L;EADBETTER, W. F.: J. Urol., 42: 14--20, 1939. CoLBY, F. H.: Essential Urology. Baltimore: Williams and Wilkins Co., 1950, pp. 252--254. GIANI, R.: Beitr. z. path. Anat. u. z. allg. Path., 42: 1-22, 1907. HERXHEIMER, G.: Arch. f. path. Anat. 185: 52--117, 1906. HINMAN, F., JOHNSON, C. M. AND JVIcCoRKLE, J. H.: J. Urol., 35: 174-189, 1936. JOELSON, J. J.: Arch. Surg., 28: 1570-1583, 1929. KINDALL, L.: J. Urol., 29: 645-659, 1933. KoPP, J. H.: J. Urol., 56: 28-34, 1946. VON LIMBECK, R.: Zschr. f. Heilk., 8: 55-66, 1887. MoRGAGNI, J.B.: De sedibus et causis morborum per anatomen indagatis, libri quinque. Venice: Remondini Press, 1761, Book 3, epistle 42, article 2 and epistle 44, article 15. MORSE, H. D.: Am. J. Path., 4: 33-49, 1928. PATCH, F. S.: New Eng. J. Med., 220: 979-985, 1939. TOULSON, H. H.: Trans. Am. Assoc. Genito Urin. Surg., 35: 191-194, 1942. WARRICK, W. D.: J. Urol. 45: 835--843, 1941.
Vol. 68, No. 5, November 1952 Printed in U.S.A.
URETERITIS CYSTICA: TREATMENT WITH SULFADIAZINE, PENICILLIN AND AUREOMYCIN REPORT OF A CASE B.G. CLARKE From the Departments of Urology, New Haven Hospital and Yale University School of Medicine, New Haven, Conn.
A case of ureteritis cystica in which the lesions disappeared and a sustained remission was produced by treatment with antibiotics has been studied. Our purpose in reporting this case is, first, to offer an observation relevant to the long discussed question of the pathogenesis of this condition; and second, to record a satisfactory therapeutic response. The literature contains only a few reports of successful treatment of this disease and none which we can discover by antibiotics. Morgagni, in 1761, described ureteritis cystica for the first time and noted its association with urinary tract inflammation. He observed "hydatids" within the ureters of two old men who had died with urinary tract inflammation associated in one case with what today would have been recognized as prostatism and in the other with posterior urethral stricture. In 1887 von Limbeck's microscopic studies showed that these lesions are multiple, small, subepithelial cysts, lined with cuboidal or transitional epithelium and anatomically indistinguishable from the structures found in cystitis cystica. In the same material he found downward sprouts of epithelium which he postulated assumed cystic form. Von Brunn, 6 years later, gave the name of cell nests to these epithelial sprouts as they appeared when separated from the parent epithelial layer. Herxheimer, reviewing his own material and the collected observations of others in 1906, recognized epithelial sprouts, cell nests, and the cysts as progressive phases of a proliferative response of urinary tract epithelium to chronic inflammation. Giani, in the same year, reported having reproduced the lesions of cystitis cystica experimentally by inducing chronic inflammation within the bladders of rabbits. Utilizing cystoscopic observations, Hinman, Johnson and McCorkle recognized the association of cystitis cystica with inflammatory conditions of the urinary tract. Warrick successfully demonstrated bacterial infection in twenty of twenty-eight cases of the same disease, with E. coli as the commonest organism. The development of urography has made recognition of ureteropyelitis cystica possible in the living patient. Little however is known of the natural history of the disease and from the few published reports available it is difficult to construct a characteristic clinical picture because the symptoms do not differ specifically from those of other inflammatory or obstructive lesions of the urinary tract. The writer acknowledges his gratitude to Dr. Clyde L. Deming, Professor of Urology in the Yale University School of Medicine for aid in preparation of the report; to Dr. Arnold H. Janzen, Professor of Radiology for critical scrutiny of the radiographic evidence; and to Dr. Michael S. Hovenanian, former Instructor in Urology for guidance in management of the case,
815
816
B. G. CLARKE
It is of interest that in 1934 Hinman and his associates concluded that "the first step in the treatment of the condition is obviously the removal of the source or cause of the inflammatory process." Five years later, Burkland and Leadbetter produced symptomatic improvement in a case of pyelo-ureteritis and cystitis cystica with pure cultures of H. influenzae by treatment with sulfanilamide but could not eradicate the organism permanently from the urine. Toulson reported having treated 2 patients with ureteritis cystica with sulfaniazine without effect. Kindall had brought about disappearance of the lesions in one case by placement of large ureteral catheters for 3 days followed by injection of silver nitrate. Kopp treated a case in similar manner with success. There are a number of reported instances of resection of the involved portion of the upper urinary tract for ureteropyelitis cystica. Our patient was a man in whom obstruction of the calyces of the right kidney had been produced by a process identified by excretory and retrograde pyelography as typical pyelo-ureteritis cystica. The history was consistent with the presence of chronic lower urinary tract infection. Because he had been given penicillin a half day before he came under our care, bacteriologic identification of the upper urinary tract invader was impossible and a combination of drugs was used. Within 2 days he was free of fever and pain, and within 9 days urograms showed that his upper urinary tract had returned to normal. He remained well during a year of observation, at the end of which his urograms were normal and his urine uninfected. CASE REPORT
A 29 year old man (L. G., 035611) was admitted to New Haven Hospital on July 30, 1950, because of constant right lower abdominal pain radiating to the right testis accompanied by vomiting. He had had gonorrhea 10 years before admission and 2 weeks before being referred to us a second attack of the same disease had been treated with penicillin with prompt relief. Three days before he came to the hospital, burning micturition and a slight urethral discharge had recurred. A short time after the onset of his pain on the day of admission he had been seen by a physician who had found gonococci in a smear of the prostatic secretion and administered an injection of penicillin. Because of persistent pain and vomiting he came to the hospital 6 hours later. At the time of admission he was uncomfortable and flushed. Temperature was 99.4 orally, pulse 90 and blood pressure 136/102. Abnormal physical findings were otherwise limited to deep tenderness in the right hypogastrium. His red blood cell count was 6.0 million, hemoglobin 16.0 gm., white blood cell count 14,000 with 85 per cent polymorphonuclear forms, 12 per cent lymphocytes, 2 per cent monocytes and 1 per cent eosinophils. The urine was of amber, smoky appearance, with a pH of 8.0, and contained no albumin or sugar. One hundred red blood cells and 5 white blood cells were seen in the high power field of the centrifuged sediment although no organisms were noted in the stained smear or subsequently reported in cultures. The blood nonprotein nitrogen and an x-ray of the abdomen were normal.
URETERITIS CYSTICA
817
The findings presented by this patient were regarded as consistent with either acute pyelonephritis with or without ureteral obstruction, or acute appendicitis, and consultants agreed upon overnight observation. Seventeen hours after the pain had begun, an excretory urogram showed a normal left upper urinary tract, but tubular diodrast excretion on the right side blocked within the pelvis (fig. 1, A). Cystoscopy revealed an easily dilated posterior urethral stricture, moderate trigonal hypertrophy, and a right ureteral meatus which was not seen to excrete urine. The ureteral catheter (No. 5F) was introduced on the right side with difficulty. Fluid irrigated from the right pelvis contained no organisms in smear or culture, and the left kidney urine was sterile. Phenolsulfonphthalein excretion
FrG. 1. A, excretory urogram 1 hour after injection of diodrast. Dye appears within kidney but does not fill pelvis or ureter. B, retrograde pyelogram. Small spherical filling defects throughout right ureter and a similar process deforming shadow of right pelvis. C, retrograde pyelogram after 14 days of treatment. Right upper urinary tract is now normal. Pressure of injection resulted in some pyelotubular reflux.
from the right kidney was nil; from the left the dye appeared in 3 minutes with secretion of 20 per cent in 15 minutes. The pyelo-ureterogram on the right showed many small spherical filling defects in the ureter with obstruction at the calyces by a similar process (fig. 1, B). The left pyelo-ureterogram was normal. For the next 14 days treatment consisted of daily doses of 2 0 gm. of sulfadiazine and 1.0 gm. of aureomycin orally, and 600,000 units of procaine penicillin intramuscularly. In 36 hours the patient was free of abdominal pain and in 48 his fever had subsided. On the ninth day an excretory urogram showed normal dye excretion on both sides with disappearance of pyelo-ureteritis cystica. Retrograde examination on the fourteenth day showed normal pyelo-ureteral
818
B. G. CLARKE
shadows (fig. 1, C), no infection in either kidney, and normal phthalein excretion from both kidneys. At the end of a year, during which he had remained well, the patient permitted examination by excretory urography which was normal. The urine remained sterile. SUMMARY
A case is reported in which renal obstruction was produced by pyelo-ureteritis cystica on the right side. Under treatment with sulfadiazine, aureomycin and penicillin there was prompt relief of obstruction and disappearance of the lesions. After a year the upper urinary tracts remained normal. Evidence in this case corroborates the inflammatory pathogenesis of pyeloureteritis cystica and suggests that further trials of antibiotics may be warranted in this condition.
943 Oak St., Winnetka, Ill. REFERENCES BoTHE, A. E., AND CmsToL, D.S.: Am. J. Roentgenol., 48: 787-793, 1942. VON BRUNN, A.: Arch. f. mik. Anat., 41: 294-302, 1893. BURKLAND, C. E. AND L;EADBETTER, W. F.: J. Urol., 42: 14--20, 1939. CoLBY, F. H.: Essential Urology. Baltimore: Williams and Wilkins Co., 1950, pp. 252--254. GIANI, R.: Beitr. z. path. Anat. u. z. allg. Path., 42: 1-22, 1907. HERXHEIMER, G.: Arch. f. path. Anat. 185: 52--117, 1906. HINMAN, F., JOHNSON, C. M. AND JVIcCoRKLE, J. H.: J. Urol., 35: 174-189, 1936. JOELSON, J. J.: Arch. Surg., 28: 1570-1583, 1929. KINDALL, L.: J. Urol., 29: 645-659, 1933. KoPP, J. H.: J. Urol., 56: 28-34, 1946. VON LIMBECK, R.: Zschr. f. Heilk., 8: 55-66, 1887. MoRGAGNI, J.B.: De sedibus et causis morborum per anatomen indagatis, libri quinque. Venice: Remondini Press, 1761, Book 3, epistle 42, article 2 and epistle 44, article 15. MORSE, H. D.: Am. J. Path., 4: 33-49, 1928. PATCH, F. S.: New Eng. J. Med., 220: 979-985, 1939. TOULSON, H. H.: Trans. Am. Assoc. Genito Urin. Surg., 35: 191-194, 1942. WARRICK, W. D.: J. Urol. 45: 835--843, 1941.