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Eosinophilic Cystitis in Children: A Self-Limited Process
OS22-5347 /84/1316-0117$0'.2.00/0 THE JGURNAL '.}F UROLOGY
Copyright© 1984 by The Wiliiams & Wilkins Co.
EOSINOPHILIC CYSTITIS MICHAEL SUTPHIN
CHILDREN: A SELF-LIMITED PROCESS AND
ANTHONY W. MIDDLETON, JR*
From the Divisions of Urology, Primary Children's Medical Center and University of Utah College of Medicine, Salt Lake City, Utah
ABSTRACT
We report a case of eosinophilic cystitis in a 7-year-old boy. Bilateral hydronephrosis and a lesion involving most of the bladder were seen initially. Complete resolution of all symptoms occurred within 3 weeks and the x-ray findings returned to normal in 6 weeks without specific therapy. A review of all reported cases of eosinophilic cystitis in children suggests that, unlike in adults, the disease is self-limited. Eosinophilic cystitis is an uncommon inflammatory process seen in children and adults. The etiology is unknown, although the disease has been associated with several different processes. We report an interesting case in a child and make observations on treatment and etiology. CASE REPORT
A 7-year-old boy presented with a 5-day history of gross hematuria, with clots, mild dysuria and frequency. There was no history of allergy or genitourinary problems. Physical examination was normal but rectal examination revealed a spongy, large mass anteriorly. An excretory urogram showed left ureteral obstruction (fig. 1, A) and a cystogram revealed bilateral ureteral reflux with a filling defect on the left base of the bladder (fig. 2, A). Urinalysis showed 1 to 2 white blood cells per high power field and red blood cells too numerous to count. Complete blood count was normal except for 7 per cent eosinophils. The blood chemistry screen and a chest x-ray were normal. Urine culture for aerobes, anaerobes or acid-fast bacillus yielded no growth. Cystoscopy revealed severe diffuse mucosa! changes with multiple areas of irregularly raised erythematous lesions involving the entire left bladder floor, both side walls and the dome of the bladder near the bladder neck. A large lesion near the left ureteral orifice appeared to be infiltrating. Transurethral biopsies revealed some focal hyperplasia of the epithelium, with intense submucosal infiltration by eosinophilic leukocytes, No malignant changes were seen. Postoperatively, the suffered right flank pain and a computerized scan showed new hydronewith increased hydronephrosis on the on the side gross hematuria and the suspicion of malignancy led to a repeat transmethral biopsy and, finally, an open At exploration a firm mass along the bladder dome and side wall was with marked thickening of the bl.adder wall. Microscopic examination showed infiltration of eosinophils, with some relatively discrete foci and areas of diffuse involvement (fig. A number of small lymphocytes, probably mast cells, were seen along with hyperplastic endothelial cells in numerous capillaries. Electron microscopy added no new information. Following open biopsy the patient suffered profuse watery diarrhea. Repeated stool cultures salmonella, shigella, Campylobacter and Yersinia were negative. Stool leukocytes were numerous, with 10 per cent eosinophils. Serum anti-A and antiB titers were 1:256 and 1:128, respectively. The patient was treated with intravenous fluid replacement and a liquid diet. No steroid or antihistamine therapy was given. The clinical condition of the patient improved rapidly
wr
Accepted for publication February 24, 1984. * Requests for reprints: 1060 East 1st South, Salt Lake City, Utah 84102. 117
FIG. L B, normal
IVP at hospitalization reveals left ureteral obstruction. 6 weeks later.
and the diarrhea resolved in 3 days. The urine was grossly clear when he was discharged from the hospital 2 days later and the patient was asymptomatic. A followup IVP and cystogram 6 weeks later were normal (figs. 1, B and 2, B). The patient has remained asymptomatic for >1 year. DISCUSSION
Eosinophilic cystitis was described first by Brown in 1960. 1 Since that time at least 40 cases have been reported in the literature 2 and other cases have been encountered but not published. Irritative bladder symptoms are the most common presentation and the disease is seen in children and adults. Eosinophilic cystitis has been described in acute, chronic and recurrent manifestations, and can mimic bladder neoplasms, interstitial cystitis and tuberculosis.
118
SUTPHIN AND MIDDLETON
A history of allergic disease has been obtained in some cases. Several investigators have suggested an allergic reaction as the etiology but the relationship is not demonstrable in a number of reported cases.'3• 4 Extensive immunologic testing has been attempted with varying results and a long list of associated allergens has been compiled_ 5 - 7 However, firm cause-and-effect relationships are lacking. 8 Gregg and Utz reported on 2 adults with eosinophilic cystitis associated with eosinophilic gastroenteritis. 9 A similar association is suggested in our case. Perlmutter and associates described a case in which a Toxocara cati bladder infestation was found, suggesting a parasitic origin of the eosinophilic cystitis. 10 Eosinophilic cystitis may occur more frequently than suspected, and may be overlooked clinically and microscopically. Hellstrom and associates described 16 cases in older men, which were associated with other conditions of the prostate or bladder, such as previous surgery, benign prostatic hyperplasia or carcinoma.11 They noted that an eosinophilic inflammatory response in the presence of other inflammatory conditions could be overlooked easily, with the investigator looking instead for malignancy, interstitial cystitis, tuberculous disease or other lesions more common than eosinophilic cystitis. Therapy has been empiric in the past. Steroids and antihisTABLE
Reference Perlmutter and associates 10 Wenzl and associates 16 Farber and Vawter 15 Champion and Ackles 14 Kessler and associates 8 Present case
tamines frequently have been used because of the suggested immunologic association. 2' 12 Desensitization therapy has been tried in some chronic cases. Sidh and associates reported on 3 adults requiring aggressive surgical intervention, including supravesical urinary diversion. 13 In our review we found that most cases of eosinophilic cystitis in children are self-limited and require no specific therapy. Table 1 is a compilation of presenting symptoms and clinical findings in our case and in all previously reported cases in children. In all but 1 case resolution was rapid and complete, occurring in 2 to 12 weeks. 8 • 10• 14- 16 The single exception, reported by Wenzl and associates, suffered 3 recurrences during 10 months. 16 Table 2 compares the treatment and outcome of the children studied. The majority of the patients improved without the use of steroids or major surgical intervention. It seems that eosinophilic cystitis in this age group is short-lived and self-limited, and symptomatic supportive treatment is all that is necessary. Should the history or laboratory studies suggest a parasitic etiology, specific treatment may be indicated. Eosinophilic cystitis has been associated variously with allergic responses, parasitic infestations and various other pathological entities of the bladder and prostate. This would seem
1. Presentation of eosinophilic cystitis in children
Pt. Age-Sex
Hematuria
Frequency
Pyuria
Pain
Obstruction
8-M 6-F 3-F 3-M 2-F 12-M 5-F 7-M
0
+
0 0
0
0 0
+ + + + + + +
0
+ +
+ ?
+ +
0
+ 0
0 0
+
+ + + +
+
0 0 0
+ +
+ ? ?
FIG. 2. · A, cystogram at hospitalization reveals bilateral ureteral reflux with filling defect on left base of bladder. B, normal cystogram 6 weeks later.
FIG. 4. Biopsy reveals infiltration of eosinophils, with some discrete foci and areas of diffuse involvement.
TABLE 2.
Treatment and results in children with eosinophilic cystitis
Reference Perlmutter and associates 10 Wenzl and
Steroids
Resolved
0
Recurrences
?
0
x 10 mos. Resolved
4
Resolved Resolved
? 2
+
Resolved Resolved
8 2
0
Resolved
6
0 (stibophen) Champion and Ackles"
+ 0
FIG. 3. CT scan 1 week after hospitalization reveals new hydronephrosis on right side and increased hydronephrosis on left side.
Kessler and associates8 Present case
Interval to Resolution (wks.)
0
associates 16
Farber and Vawter 15
Outcome
12
.80SI~l0PHIL1C CV"E1T1TIS
to that the 1ntlam1mf,to,ry tesponse seen in this may be a common manifestation several differing etiologic pathways. Interestingly, the etiology of the condition in all but 1 of the previously reported children is unknown and all of these children had complete and rapid resolution of the disease except for 1, whose disease lasted for 10 months. 16 In summary, a case of eosinophilic cystitis in a child with probable associated eosinophilic gastroenteritis is presented. The disorder resolved rapidly and completely with supportive and symptomatic therapy only. A review of the reported cases in children leads us to conclude that eosinophilic cystitis in children is self-limited and generally requires no specific therapy. REFERENCES
1. Brown, E.W.: Eosinophilic granuloma of the bladder. J. Urol., 83:
665, 1960. 2. Littleton, R.H., Farah, R. N. and Cerny, J.C.: Eosinophilic cystitis: an uncommon form of cystitis. J. Urol., 127: 132, 1982. 3. Marshall, F. F. and Middleton, A. W., Jr.: Eosinophilic cystitis. J. Urol., 112: 335, 1974. 4. Rubin, L. and Pincus, M. B.: Eosinophilic cystitis: the relationship of allergy in the urinary tract to eosinophilic cystitis and the pathophysiology of easinaphilia. J. Ural., 112: 457, 1974.
E.
6. 7.
8. 9. 10. 11. 12. 13.
14. 15.
16.
119
CH:ILDHEN
!·,L B. Powell E B. Tho1nas 0. C., Queng, J. T. and J. P.: Allergy of the lower urinary tract. J. Ural., Hi7: 631, 1972. Frensilli, F. J., Sache1, E. C. and Keegan G. T,: Eosinophilic observations on etiology. J. Ural., Hl7: 595, 1972. uc,iu,,ct:1,11 M.: Eosinophilic cystitis. J. Urn!., 106: 854, 1971. Kessler, W. 0., Clark, P. L. and Kaplan, G. W.: Eosinophilic cystitis. Urology, 6: 1975. Gregg, J. A. and Utz, D. · Eosinophilic cystitis associated with eosinophilic gastroenteritis. Mayo Clin. Proc., 49: 185, 1974. Perlmutter, A. D., Edlow, J.B. and Kevy, S. V.: Toxocara antibodies in eosinophilic cystitis. J. Ped., 73: 340, 1968. Hellstrom, H. R., Davis, B. K. and Shonnard, J. W.: Eosinophilic cystitis. A study of 16 cases. Amer. J. Clin. Path., 72: 777, 1979. Horowitz, J., Slavin, S. and Pfau, A.: Chronic renal failure due to eosinophilic cystitis. Ann. Allergy, 30: 502, 1972. Sidh, S. M., Smith, S. P., Silber, S. B. and Young, J. D., Jr.: Eosinophilic cystitis: advanced disease requiring surgical intervention. Urology, 15: 23, 1980. Champion, R. H. and Ackles, R. C.: Eosinophilic cystitis. J. Urol., 96: 729, 1966. Farber, F. and Vawter, G. F.: Clinical pathological conference. J. Ped., 62: 941, 1963. Wenzl, J.E., Greene, L. F. and Harris, L. E.: Eosinophilic cystitis. J. Ped., 64: 746, 1964. 1
1
1
1
1
Copyright© 1984 by The Wiliiams & Wilkins Co.
EOSINOPHILIC CYSTITIS MICHAEL SUTPHIN
CHILDREN: A SELF-LIMITED PROCESS AND
ANTHONY W. MIDDLETON, JR*
From the Divisions of Urology, Primary Children's Medical Center and University of Utah College of Medicine, Salt Lake City, Utah
ABSTRACT
We report a case of eosinophilic cystitis in a 7-year-old boy. Bilateral hydronephrosis and a lesion involving most of the bladder were seen initially. Complete resolution of all symptoms occurred within 3 weeks and the x-ray findings returned to normal in 6 weeks without specific therapy. A review of all reported cases of eosinophilic cystitis in children suggests that, unlike in adults, the disease is self-limited. Eosinophilic cystitis is an uncommon inflammatory process seen in children and adults. The etiology is unknown, although the disease has been associated with several different processes. We report an interesting case in a child and make observations on treatment and etiology. CASE REPORT
A 7-year-old boy presented with a 5-day history of gross hematuria, with clots, mild dysuria and frequency. There was no history of allergy or genitourinary problems. Physical examination was normal but rectal examination revealed a spongy, large mass anteriorly. An excretory urogram showed left ureteral obstruction (fig. 1, A) and a cystogram revealed bilateral ureteral reflux with a filling defect on the left base of the bladder (fig. 2, A). Urinalysis showed 1 to 2 white blood cells per high power field and red blood cells too numerous to count. Complete blood count was normal except for 7 per cent eosinophils. The blood chemistry screen and a chest x-ray were normal. Urine culture for aerobes, anaerobes or acid-fast bacillus yielded no growth. Cystoscopy revealed severe diffuse mucosa! changes with multiple areas of irregularly raised erythematous lesions involving the entire left bladder floor, both side walls and the dome of the bladder near the bladder neck. A large lesion near the left ureteral orifice appeared to be infiltrating. Transurethral biopsies revealed some focal hyperplasia of the epithelium, with intense submucosal infiltration by eosinophilic leukocytes, No malignant changes were seen. Postoperatively, the suffered right flank pain and a computerized scan showed new hydronewith increased hydronephrosis on the on the side gross hematuria and the suspicion of malignancy led to a repeat transmethral biopsy and, finally, an open At exploration a firm mass along the bladder dome and side wall was with marked thickening of the bl.adder wall. Microscopic examination showed infiltration of eosinophils, with some relatively discrete foci and areas of diffuse involvement (fig. A number of small lymphocytes, probably mast cells, were seen along with hyperplastic endothelial cells in numerous capillaries. Electron microscopy added no new information. Following open biopsy the patient suffered profuse watery diarrhea. Repeated stool cultures salmonella, shigella, Campylobacter and Yersinia were negative. Stool leukocytes were numerous, with 10 per cent eosinophils. Serum anti-A and antiB titers were 1:256 and 1:128, respectively. The patient was treated with intravenous fluid replacement and a liquid diet. No steroid or antihistamine therapy was given. The clinical condition of the patient improved rapidly
wr
Accepted for publication February 24, 1984. * Requests for reprints: 1060 East 1st South, Salt Lake City, Utah 84102. 117
FIG. L B, normal
IVP at hospitalization reveals left ureteral obstruction. 6 weeks later.
and the diarrhea resolved in 3 days. The urine was grossly clear when he was discharged from the hospital 2 days later and the patient was asymptomatic. A followup IVP and cystogram 6 weeks later were normal (figs. 1, B and 2, B). The patient has remained asymptomatic for >1 year. DISCUSSION
Eosinophilic cystitis was described first by Brown in 1960. 1 Since that time at least 40 cases have been reported in the literature 2 and other cases have been encountered but not published. Irritative bladder symptoms are the most common presentation and the disease is seen in children and adults. Eosinophilic cystitis has been described in acute, chronic and recurrent manifestations, and can mimic bladder neoplasms, interstitial cystitis and tuberculosis.
118
SUTPHIN AND MIDDLETON
A history of allergic disease has been obtained in some cases. Several investigators have suggested an allergic reaction as the etiology but the relationship is not demonstrable in a number of reported cases.'3• 4 Extensive immunologic testing has been attempted with varying results and a long list of associated allergens has been compiled_ 5 - 7 However, firm cause-and-effect relationships are lacking. 8 Gregg and Utz reported on 2 adults with eosinophilic cystitis associated with eosinophilic gastroenteritis. 9 A similar association is suggested in our case. Perlmutter and associates described a case in which a Toxocara cati bladder infestation was found, suggesting a parasitic origin of the eosinophilic cystitis. 10 Eosinophilic cystitis may occur more frequently than suspected, and may be overlooked clinically and microscopically. Hellstrom and associates described 16 cases in older men, which were associated with other conditions of the prostate or bladder, such as previous surgery, benign prostatic hyperplasia or carcinoma.11 They noted that an eosinophilic inflammatory response in the presence of other inflammatory conditions could be overlooked easily, with the investigator looking instead for malignancy, interstitial cystitis, tuberculous disease or other lesions more common than eosinophilic cystitis. Therapy has been empiric in the past. Steroids and antihisTABLE
Reference Perlmutter and associates 10 Wenzl and associates 16 Farber and Vawter 15 Champion and Ackles 14 Kessler and associates 8 Present case
tamines frequently have been used because of the suggested immunologic association. 2' 12 Desensitization therapy has been tried in some chronic cases. Sidh and associates reported on 3 adults requiring aggressive surgical intervention, including supravesical urinary diversion. 13 In our review we found that most cases of eosinophilic cystitis in children are self-limited and require no specific therapy. Table 1 is a compilation of presenting symptoms and clinical findings in our case and in all previously reported cases in children. In all but 1 case resolution was rapid and complete, occurring in 2 to 12 weeks. 8 • 10• 14- 16 The single exception, reported by Wenzl and associates, suffered 3 recurrences during 10 months. 16 Table 2 compares the treatment and outcome of the children studied. The majority of the patients improved without the use of steroids or major surgical intervention. It seems that eosinophilic cystitis in this age group is short-lived and self-limited, and symptomatic supportive treatment is all that is necessary. Should the history or laboratory studies suggest a parasitic etiology, specific treatment may be indicated. Eosinophilic cystitis has been associated variously with allergic responses, parasitic infestations and various other pathological entities of the bladder and prostate. This would seem
1. Presentation of eosinophilic cystitis in children
Pt. Age-Sex
Hematuria
Frequency
Pyuria
Pain
Obstruction
8-M 6-F 3-F 3-M 2-F 12-M 5-F 7-M
0
+
0 0
0
0 0
+ + + + + + +
0
+ +
+ ?
+ +
0
+ 0
0 0
+
+ + + +
+
0 0 0
+ +
+ ? ?
FIG. 2. · A, cystogram at hospitalization reveals bilateral ureteral reflux with filling defect on left base of bladder. B, normal cystogram 6 weeks later.
FIG. 4. Biopsy reveals infiltration of eosinophils, with some discrete foci and areas of diffuse involvement.
TABLE 2.
Treatment and results in children with eosinophilic cystitis
Reference Perlmutter and associates 10 Wenzl and
Steroids
Resolved
0
Recurrences
?
0
x 10 mos. Resolved
4
Resolved Resolved
? 2
+
Resolved Resolved
8 2
0
Resolved
6
0 (stibophen) Champion and Ackles"
+ 0
FIG. 3. CT scan 1 week after hospitalization reveals new hydronephrosis on right side and increased hydronephrosis on left side.
Kessler and associates8 Present case
Interval to Resolution (wks.)
0
associates 16
Farber and Vawter 15
Outcome
12
.80SI~l0PHIL1C CV"E1T1TIS
to that the 1ntlam1mf,to,ry tesponse seen in this may be a common manifestation several differing etiologic pathways. Interestingly, the etiology of the condition in all but 1 of the previously reported children is unknown and all of these children had complete and rapid resolution of the disease except for 1, whose disease lasted for 10 months. 16 In summary, a case of eosinophilic cystitis in a child with probable associated eosinophilic gastroenteritis is presented. The disorder resolved rapidly and completely with supportive and symptomatic therapy only. A review of the reported cases in children leads us to conclude that eosinophilic cystitis in children is self-limited and generally requires no specific therapy. REFERENCES
1. Brown, E.W.: Eosinophilic granuloma of the bladder. J. Urol., 83:
665, 1960. 2. Littleton, R.H., Farah, R. N. and Cerny, J.C.: Eosinophilic cystitis: an uncommon form of cystitis. J. Urol., 127: 132, 1982. 3. Marshall, F. F. and Middleton, A. W., Jr.: Eosinophilic cystitis. J. Urol., 112: 335, 1974. 4. Rubin, L. and Pincus, M. B.: Eosinophilic cystitis: the relationship of allergy in the urinary tract to eosinophilic cystitis and the pathophysiology of easinaphilia. J. Ural., 112: 457, 1974.
E.
6. 7.
8. 9. 10. 11. 12. 13.
14. 15.
16.
119
CH:ILDHEN
!·,L B. Powell E B. Tho1nas 0. C., Queng, J. T. and J. P.: Allergy of the lower urinary tract. J. Ural., Hi7: 631, 1972. Frensilli, F. J., Sache1, E. C. and Keegan G. T,: Eosinophilic observations on etiology. J. Ural., Hl7: 595, 1972. uc,iu,,ct:1,11 M.: Eosinophilic cystitis. J. Urn!., 106: 854, 1971. Kessler, W. 0., Clark, P. L. and Kaplan, G. W.: Eosinophilic cystitis. Urology, 6: 1975. Gregg, J. A. and Utz, D. · Eosinophilic cystitis associated with eosinophilic gastroenteritis. Mayo Clin. Proc., 49: 185, 1974. Perlmutter, A. D., Edlow, J.B. and Kevy, S. V.: Toxocara antibodies in eosinophilic cystitis. J. Ped., 73: 340, 1968. Hellstrom, H. R., Davis, B. K. and Shonnard, J. W.: Eosinophilic cystitis. A study of 16 cases. Amer. J. Clin. Path., 72: 777, 1979. Horowitz, J., Slavin, S. and Pfau, A.: Chronic renal failure due to eosinophilic cystitis. Ann. Allergy, 30: 502, 1972. Sidh, S. M., Smith, S. P., Silber, S. B. and Young, J. D., Jr.: Eosinophilic cystitis: advanced disease requiring surgical intervention. Urology, 15: 23, 1980. Champion, R. H. and Ackles, R. C.: Eosinophilic cystitis. J. Urol., 96: 729, 1966. Farber, F. and Vawter, G. F.: Clinical pathological conference. J. Ped., 62: 941, 1963. Wenzl, J.E., Greene, L. F. and Harris, L. E.: Eosinophilic cystitis. J. Ped., 64: 746, 1964. 1
1
1
1
1