VoL
THll JoUllNAL oF UEowo11
Copyright © 1977 by The Williams & Wilkins Co.
November in U.S.A.
INTERSTITIAL CYSTITIS IN ADOLESCE:f'.\JT GIRLS AMICUR FARKAS,* JERRY WAISMAI\J'
AND
WILLARD E. GOODWIN
From the Departments of Surgery/Urology and Pathology, University of California School of Medicine, Los Angeles, California
ABSTRACT
Two cases of interstitial cystitis with typical, large bladder ulcerations in adolescent girls are reported. The specific diagnosis was confirmed histologicaHy after full-thickness segmental :resection of the bladder wall at the site of the ulceration during subsequent operations. Contrary to other reports based on subjective clinical findings, interstitial cystitis in children is rare when rigid criteria, including careful histological study, are applied. Treatment in children is the same as in adults and should be conservative. A conscientious attempt should be made to exclude infection and tuberculosis as possible contributors to the symptoms of urinary frequency and discomfort, as well as other causes of blad.de:r abnormality. If conservative management fails to relieve symptoms the bl.adder may enlarged in sorn.e cases by using a segment of intestine. Interstitial cystitis has been recognized for almost a cen" 2 Its characteristic presentation as an idiopathic ulcer bladder received popular attention after publication of Hunner's description 60 years ago. 3 During the intervening years this condition has been discussed widely in the medical and v,c, 5 ,.,u, literature with regard to its symptomatology, etiology, cystoscopic and histologic findings, as well as modalities for treatment. The disease is seldom described in children.4-9 Herein we report on 2 young girls who presented with bladder ulcerations.
bladder wall, including the large ulcer, was Changes were described by the pathologist as being consistent with interstitial cystitis (Runner's ulcer)o . Pathology: The specimen of bladder taken during 0m,rnq,r;•,nv in March 1975 disclosed extensive necrosis with fibrin and granulocytes. No intact epithelium was only granulation tissue and a few smooth muscle cells. A piece of bladder wall, measuring 4.0 by 3.0 2.0 was removed in April 1975. The epithelium was red glistening with a central ulcer that measured 1.3 cm. m diameter with a yellow, shaggy base. CASE REPORTS deep ulcer was coated with erythrocytes, fibrin, Case 1 A 14-year-old white girl, UCLA 082 86 38, was and granulocytes (fig. 2). Throughout the wall dense fibrous 3, A). referred for consultation and treatment of continual urinary tissue separated the bundles of smooth muscle since childhood. The patient had been in good Strands of fibrous tissue extended into the bundles muscle general health until she was 10 years old when abdominal and, in some areas, replaced the muscle. The scar was discomfort, suprapubic pain, increasing urinary frequency limited to the immediate region of the ulcer but was observed and intermittent hematuria occurred. Repeated urine exami- at the edges of the segment of bladder. Perivesical nations revealed only pyuria and there was no growth of tissue also was scarred. Lymphocytes, arranged bacteria on cultures. When she ·,vas 12 years old a complete in follicles, were prevalent, while plasma cells and ro1to2:ic1H study was performed elsewhere, including an excre- were found in lesser numbers. With use of an tory urogram (IVP) and voiding urethrocystogram, which stain many mast cells were found in the fibrous tissue were normal. Cystoscopy disclosed cystitis and urethral ste- B). Convalescence was uneventful. At rnOlmunn 6 months later nosis. Urethral dilatation was done at that time and subsebut the patient continued to suffer from severe uri- the patient had resumed nearly normal urinary habits. She tr,,,,,."'"'"" and hematuria. In 1975 a repeat cystoscopy no longer had frequency, urgency or bleeding, and a large ulceration on the right lateral wall of the was negative. The bladder apparently had neously after removal of the ulcer. Case 2 A 19-year-olcl. black girl, UCLA 060 57 was in excellent health, except for dysuria and hematuria. Repeated urine cultures, referred to us in 1971 after a long and complicated , •.,,.-~•.,,., acid-fast studies for tuberculosis, showed no growth. history. When she was 15 years old dysuria, frequency and An IVP was normal and a cystogram showed a deformity on hematuria developed. Urological evaluation elsewhere the side of the bladder (fig. 1). Cystoscopy revealed a included urine cultures, IVP and cystourethrogram, as well small capacity bladder (90 cc) with cracking of the mucosa as cultures for acid-fast bacilli. All of these studies were and bleeding appeared when the bladder was distended. There normal and there was no evidence of gTowth in the was a large ulcer, 2.5 cm. in diameter, located on the right specimens. A year later cystoscopy revealed an ulceration side of the bladder, superior and lateral to the right ureteral the base of the bladder. A repeat cystoscopy showed a small capacity bladder orifice. A cup biopsy of this area demonstrated changes that suggested interstitial cystitis. Further studies, including up- multiple ulcerations, the largest above the trigone, per gastrointestinal series and barium enema, were done to by 1 observer to be a fistula between the uterus and rule out any intra-abdominal condition as a possible contrib- bladder. A barium enema was normal. At cause. All of these studies were reported as normal. In intra-abdominal viscera and genitalia were normal and 1975 exploration revealed normal abdominal viscera transvesical resection of the ulcerated area was done. The internal genitalia. A wide, full-thickness excision of the specimen showed inflammatory changes consistent with inter·· stitial cystitis. Pathology: The segment of bladder taken Accepted for publication December 17, 1976. *Current address: Department of Urology, khilov Hospital and in August 1971 measured 3.0 by 2.5 by luminal surface was covered congested mucosa. the University of Tel Aviv School of Medicine, Tel Aviv, Israel. 0
0
837
838
FARKAS, WAISMAN AND GOODWIN
vesicoureteral reflux worsened with evidence of dilatation of the upper urinary tract. In June 1975 most of the diseased portion of the bladder was removed and the bladder was enlarged with a "cup-patch" ileocystoplasty. 10 Pathology: The removed specimen of the bladder wall measured 1.5 by 0.8 by 0.6 cm. The bladder muscle was replaced extensively by scar tissue that contained clusters of lymphocytes and mast cells in increased numbers. Perivesical adipose tissue also was inflamed. Convalescence was uneventful but the followup has been less than satisfactory. The patient still suffers extreme urgency and frequency, although the bladder capacity had been increased to approximately 300 cc by the cystoplasty. Urinary tract infection with E. coli and other organisms persists. Most of the pain has disappeared with the increased bladder capacity. Recently, because of the persistence of urinary frequency the patient was referred to Dr. Thomas Stamey at Stanford University Hospital for evaluation from February 29 to March 5, 1976. The cystoscopic findings of interstitial cystitis were confirmed and a repeat biopsy showed that the interstitial cystitis not only remained in the bladder but also involved a portion of the ileum that had been attached to the dome of the bladder at the time of the ileocystoplasty. In other words, the graft also had acquired the same disease, whatever that may be. In a letter discussing this diagnosis Doctor Stamey commented, "The interesting part of the biopsy was that the
Fm. 1. Case 1. Cystogram shows deformity on right side of bladder.
On microscopic examination an ulcer extended into the lamina propria, similar to the lesion described in case 1. The bulk of the scar was beneath the ulcer, although patches of excess fibrous tissue were observed deep in the bladder wall, remote from the ulcer. In these areas bundles of smooth muscle were attenuated. Clusters of lymphocytes were seen surrounding blood vessels and nerves throughout the wall. Mast cells were demonstrated but not in large numbers. Epithelium at the edges of the ulcer showed squamous metaplasia. A specimen obtained during cystoscopy in April 1972 disclosed similar changes except that lymphocytes and plasma cells dominated the cellular component of the inflammatory reaction and more mast cells were observed. Several months later a second cystoscopic biopsy revealed squamous metaplasia with acute and chronic cystitis but no ulceration. Only mucosa was present. After the initial excision of the ulcer the patient did well for almost 2 years until she began to suffer again from severe dysuria, frequency and hematuria. In 1973 cystoscopy showed a large ulcer on the left side of the bladder and a cystogram demonstrated left vesicoureteral reflux. She also had urinary tract infection with Escherichia coli and other coliform organisms. A cup biopsy from the ulcer was obtained. The patient was treated conservatively with steroids and periodic hydraulic dilatation of the bladder because of the extreme frequency o~ing to small bladder capacity. The conservative measures failed to relieve the symptoms, however, and the
Fm. 2. Case 1. Base of ulcer is coated with fibrin and cellular debris. Smooth muscle (M) beneath is surrounded by dense fibrous tissue (F) containing inflammatory cells. H & E, reduced from xlOO.
83D
INTERSTITIAL CYSTITIS IN ADOLESCENT GIRLS
Fm. 3. Case 1. from xlOO. x250.
bundles of smooth muscle cells dense fibrous tissue (F) between
bowel which had also been included in the with the diagnosis continues on long-term antibacterial and sulfamethoxazole If rnr·mc,rv diversion
tract begins to occur, successful treatment may require cal excision of the diseased bladder wall and enlargement of the bladder with a segment have been by results of this adults but the is still unresolved disease in REFERENCES
1. Skene, A. J. C.: Cystitis. In: Diseases of the Bladder
DISCUSSION
2.
cases and Callahan ·r1cim tPrl in their series of 143 patients 7 striking contrast are the reports of McDonald and associates (45 -···-···,-·--· G Chenoweth and Clawater (7 cases) 8 and Geist 9 who have described and ,u,w•""'" (21 series of children with interstitial sent an incidence of 4.8 to 12 per cent of all "~·"-,-,,-,,,- in their The were based and in was the 0
3.
4. 5.
6. 7. 8. 9. 10. 11. 12.
Urethra in Women. New York: William Wood and Co. 167, 1878. Skene, A. J. C.: Vesico-urethral fissure. In: Diseases of Bladder and Urethra in Women. New York: William "\Nood and Co., p. 234, 1878. Hunner, G. L.: A rare type of bladder ulcer in women: report cases. Trans. South. Surg. Gynec. Ass., 27: 247, 1914. McDonald, H. P., Upchurch, W. E. and Sturdevant, C. K Interstitial cystitis in children. J. Urol., 70: 890, 1953. Bowers, J. E. and Lattimer, J. K: Interstitial cystitis. Su:rg . , Gynec. & Obst., 105: 313, 1957. McDonald, H. P., Upchurch, W. K and Artime, M.: Bladder dysfunction in children caused by intersti.tial cystitis. ,L Urnl., 80: 354, 1958. Baker, W. J. and Callahan, D. H., Jr.: Interstitial cystitis. Urol., 81: 112, 1959. Chenoweth, C. V. and Clawater, E. W., Jr.: Inte:rstitial in children. J. Urol., 83: 150, 1960. Geist, R. W. and Antolak, S. J., ck: Interstitial cystitis rn children. J. UroL, 1114: 922, 1970. Goodwin, W. E., Winter, C. C. and Barker, W. F.: "Cup-patch" technique ofil.eocystoplasty for bladder enlargement or substitution. Surg., Gynec. & Obst., 108: 240, 1959. J. H.: Personal communication. Silk, M. · Bladder antibodies in interstitial cystitis. J. U:rol., Hl3: 307, 1970.
fact that our case 2 had the same disease in the
this idea.) Partial or may decrease the anti,. of the condition. 12- 15 1ii\!henever conservative with steroids, and dilatation of the fails to relieve symp-.. deterioration of the upper
13. Jokinen, E. J., Oravisto, K. J. and Alfthan, 0. S.: The effect cystectomy on antitissue antibodies in interstitial cystitis. Clin. Exp. Immunol., 15: 457, 1973. 14. Gordon, H. L., Rossen, R. D., Hersh, K M. and Yium, J. J . : Immunologic aspects of interstitial cystitis. UroL, 109: 228, 1973. D. A.: Interstitial cystitis 15. Jacobo, E. Stamler, F. W. and 3: 481, 1974. by total cystectomy.
THll JoUllNAL oF UEowo11
Copyright © 1977 by The Williams & Wilkins Co.
November in U.S.A.
INTERSTITIAL CYSTITIS IN ADOLESCE:f'.\JT GIRLS AMICUR FARKAS,* JERRY WAISMAI\J'
AND
WILLARD E. GOODWIN
From the Departments of Surgery/Urology and Pathology, University of California School of Medicine, Los Angeles, California
ABSTRACT
Two cases of interstitial cystitis with typical, large bladder ulcerations in adolescent girls are reported. The specific diagnosis was confirmed histologicaHy after full-thickness segmental :resection of the bladder wall at the site of the ulceration during subsequent operations. Contrary to other reports based on subjective clinical findings, interstitial cystitis in children is rare when rigid criteria, including careful histological study, are applied. Treatment in children is the same as in adults and should be conservative. A conscientious attempt should be made to exclude infection and tuberculosis as possible contributors to the symptoms of urinary frequency and discomfort, as well as other causes of blad.de:r abnormality. If conservative management fails to relieve symptoms the bl.adder may enlarged in sorn.e cases by using a segment of intestine. Interstitial cystitis has been recognized for almost a cen" 2 Its characteristic presentation as an idiopathic ulcer bladder received popular attention after publication of Hunner's description 60 years ago. 3 During the intervening years this condition has been discussed widely in the medical and v,c, 5 ,.,u, literature with regard to its symptomatology, etiology, cystoscopic and histologic findings, as well as modalities for treatment. The disease is seldom described in children.4-9 Herein we report on 2 young girls who presented with bladder ulcerations.
bladder wall, including the large ulcer, was Changes were described by the pathologist as being consistent with interstitial cystitis (Runner's ulcer)o . Pathology: The specimen of bladder taken during 0m,rnq,r;•,nv in March 1975 disclosed extensive necrosis with fibrin and granulocytes. No intact epithelium was only granulation tissue and a few smooth muscle cells. A piece of bladder wall, measuring 4.0 by 3.0 2.0 was removed in April 1975. The epithelium was red glistening with a central ulcer that measured 1.3 cm. m diameter with a yellow, shaggy base. CASE REPORTS deep ulcer was coated with erythrocytes, fibrin, Case 1 A 14-year-old white girl, UCLA 082 86 38, was and granulocytes (fig. 2). Throughout the wall dense fibrous 3, A). referred for consultation and treatment of continual urinary tissue separated the bundles of smooth muscle since childhood. The patient had been in good Strands of fibrous tissue extended into the bundles muscle general health until she was 10 years old when abdominal and, in some areas, replaced the muscle. The scar was discomfort, suprapubic pain, increasing urinary frequency limited to the immediate region of the ulcer but was observed and intermittent hematuria occurred. Repeated urine exami- at the edges of the segment of bladder. Perivesical nations revealed only pyuria and there was no growth of tissue also was scarred. Lymphocytes, arranged bacteria on cultures. When she ·,vas 12 years old a complete in follicles, were prevalent, while plasma cells and ro1to2:ic1H study was performed elsewhere, including an excre- were found in lesser numbers. With use of an tory urogram (IVP) and voiding urethrocystogram, which stain many mast cells were found in the fibrous tissue were normal. Cystoscopy disclosed cystitis and urethral ste- B). Convalescence was uneventful. At rnOlmunn 6 months later nosis. Urethral dilatation was done at that time and subsebut the patient continued to suffer from severe uri- the patient had resumed nearly normal urinary habits. She tr,,,,,."'"'"" and hematuria. In 1975 a repeat cystoscopy no longer had frequency, urgency or bleeding, and a large ulceration on the right lateral wall of the was negative. The bladder apparently had neously after removal of the ulcer. Case 2 A 19-year-olcl. black girl, UCLA 060 57 was in excellent health, except for dysuria and hematuria. Repeated urine cultures, referred to us in 1971 after a long and complicated , •.,,.-~•.,,., acid-fast studies for tuberculosis, showed no growth. history. When she was 15 years old dysuria, frequency and An IVP was normal and a cystogram showed a deformity on hematuria developed. Urological evaluation elsewhere the side of the bladder (fig. 1). Cystoscopy revealed a included urine cultures, IVP and cystourethrogram, as well small capacity bladder (90 cc) with cracking of the mucosa as cultures for acid-fast bacilli. All of these studies were and bleeding appeared when the bladder was distended. There normal and there was no evidence of gTowth in the was a large ulcer, 2.5 cm. in diameter, located on the right specimens. A year later cystoscopy revealed an ulceration side of the bladder, superior and lateral to the right ureteral the base of the bladder. A repeat cystoscopy showed a small capacity bladder orifice. A cup biopsy of this area demonstrated changes that suggested interstitial cystitis. Further studies, including up- multiple ulcerations, the largest above the trigone, per gastrointestinal series and barium enema, were done to by 1 observer to be a fistula between the uterus and rule out any intra-abdominal condition as a possible contrib- bladder. A barium enema was normal. At cause. All of these studies were reported as normal. In intra-abdominal viscera and genitalia were normal and 1975 exploration revealed normal abdominal viscera transvesical resection of the ulcerated area was done. The internal genitalia. A wide, full-thickness excision of the specimen showed inflammatory changes consistent with inter·· stitial cystitis. Pathology: The segment of bladder taken Accepted for publication December 17, 1976. *Current address: Department of Urology, khilov Hospital and in August 1971 measured 3.0 by 2.5 by luminal surface was covered congested mucosa. the University of Tel Aviv School of Medicine, Tel Aviv, Israel. 0
0
837
838
FARKAS, WAISMAN AND GOODWIN
vesicoureteral reflux worsened with evidence of dilatation of the upper urinary tract. In June 1975 most of the diseased portion of the bladder was removed and the bladder was enlarged with a "cup-patch" ileocystoplasty. 10 Pathology: The removed specimen of the bladder wall measured 1.5 by 0.8 by 0.6 cm. The bladder muscle was replaced extensively by scar tissue that contained clusters of lymphocytes and mast cells in increased numbers. Perivesical adipose tissue also was inflamed. Convalescence was uneventful but the followup has been less than satisfactory. The patient still suffers extreme urgency and frequency, although the bladder capacity had been increased to approximately 300 cc by the cystoplasty. Urinary tract infection with E. coli and other organisms persists. Most of the pain has disappeared with the increased bladder capacity. Recently, because of the persistence of urinary frequency the patient was referred to Dr. Thomas Stamey at Stanford University Hospital for evaluation from February 29 to March 5, 1976. The cystoscopic findings of interstitial cystitis were confirmed and a repeat biopsy showed that the interstitial cystitis not only remained in the bladder but also involved a portion of the ileum that had been attached to the dome of the bladder at the time of the ileocystoplasty. In other words, the graft also had acquired the same disease, whatever that may be. In a letter discussing this diagnosis Doctor Stamey commented, "The interesting part of the biopsy was that the
Fm. 1. Case 1. Cystogram shows deformity on right side of bladder.
On microscopic examination an ulcer extended into the lamina propria, similar to the lesion described in case 1. The bulk of the scar was beneath the ulcer, although patches of excess fibrous tissue were observed deep in the bladder wall, remote from the ulcer. In these areas bundles of smooth muscle were attenuated. Clusters of lymphocytes were seen surrounding blood vessels and nerves throughout the wall. Mast cells were demonstrated but not in large numbers. Epithelium at the edges of the ulcer showed squamous metaplasia. A specimen obtained during cystoscopy in April 1972 disclosed similar changes except that lymphocytes and plasma cells dominated the cellular component of the inflammatory reaction and more mast cells were observed. Several months later a second cystoscopic biopsy revealed squamous metaplasia with acute and chronic cystitis but no ulceration. Only mucosa was present. After the initial excision of the ulcer the patient did well for almost 2 years until she began to suffer again from severe dysuria, frequency and hematuria. In 1973 cystoscopy showed a large ulcer on the left side of the bladder and a cystogram demonstrated left vesicoureteral reflux. She also had urinary tract infection with Escherichia coli and other coliform organisms. A cup biopsy from the ulcer was obtained. The patient was treated conservatively with steroids and periodic hydraulic dilatation of the bladder because of the extreme frequency o~ing to small bladder capacity. The conservative measures failed to relieve the symptoms, however, and the
Fm. 2. Case 1. Base of ulcer is coated with fibrin and cellular debris. Smooth muscle (M) beneath is surrounded by dense fibrous tissue (F) containing inflammatory cells. H & E, reduced from xlOO.
83D
INTERSTITIAL CYSTITIS IN ADOLESCENT GIRLS
Fm. 3. Case 1. from xlOO. x250.
bundles of smooth muscle cells dense fibrous tissue (F) between
bowel which had also been included in the with the diagnosis continues on long-term antibacterial and sulfamethoxazole If rnr·mc,rv diversion
tract begins to occur, successful treatment may require cal excision of the diseased bladder wall and enlargement of the bladder with a segment have been by results of this adults but the is still unresolved disease in REFERENCES
1. Skene, A. J. C.: Cystitis. In: Diseases of the Bladder
DISCUSSION
2.
cases and Callahan ·r1cim tPrl in their series of 143 patients 7 striking contrast are the reports of McDonald and associates (45 -···-···,-·--· G Chenoweth and Clawater (7 cases) 8 and Geist 9 who have described and ,u,w•""'" (21 series of children with interstitial sent an incidence of 4.8 to 12 per cent of all "~·"-,-,,-,,,- in their The were based and in was the 0
3.
4. 5.
6. 7. 8. 9. 10. 11. 12.
Urethra in Women. New York: William Wood and Co. 167, 1878. Skene, A. J. C.: Vesico-urethral fissure. In: Diseases of Bladder and Urethra in Women. New York: William "\Nood and Co., p. 234, 1878. Hunner, G. L.: A rare type of bladder ulcer in women: report cases. Trans. South. Surg. Gynec. Ass., 27: 247, 1914. McDonald, H. P., Upchurch, W. E. and Sturdevant, C. K Interstitial cystitis in children. J. Urol., 70: 890, 1953. Bowers, J. E. and Lattimer, J. K: Interstitial cystitis. Su:rg . , Gynec. & Obst., 105: 313, 1957. McDonald, H. P., Upchurch, W. K and Artime, M.: Bladder dysfunction in children caused by intersti.tial cystitis. ,L Urnl., 80: 354, 1958. Baker, W. J. and Callahan, D. H., Jr.: Interstitial cystitis. Urol., 81: 112, 1959. Chenoweth, C. V. and Clawater, E. W., Jr.: Inte:rstitial in children. J. Urol., 83: 150, 1960. Geist, R. W. and Antolak, S. J., ck: Interstitial cystitis rn children. J. UroL, 1114: 922, 1970. Goodwin, W. E., Winter, C. C. and Barker, W. F.: "Cup-patch" technique ofil.eocystoplasty for bladder enlargement or substitution. Surg., Gynec. & Obst., 108: 240, 1959. J. H.: Personal communication. Silk, M. · Bladder antibodies in interstitial cystitis. J. U:rol., Hl3: 307, 1970.
fact that our case 2 had the same disease in the
this idea.) Partial or may decrease the anti,. of the condition. 12- 15 1ii\!henever conservative with steroids, and dilatation of the fails to relieve symp-.. deterioration of the upper
13. Jokinen, E. J., Oravisto, K. J. and Alfthan, 0. S.: The effect cystectomy on antitissue antibodies in interstitial cystitis. Clin. Exp. Immunol., 15: 457, 1973. 14. Gordon, H. L., Rossen, R. D., Hersh, K M. and Yium, J. J . : Immunologic aspects of interstitial cystitis. UroL, 109: 228, 1973. D. A.: Interstitial cystitis 15. Jacobo, E. Stamler, F. W. and 3: 481, 1974. by total cystectomy.
