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Eosinophilic Cystitis
Vol. 106, December Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright
© 1971 by The Williams
& Wilkins Co.
EOSINOPHILIC CYSTITIS MICHAEL GOLDSTEIN From the Department of Urology, University of Texas Southwestern Medical School, Dallas, Texas
Since the first case report of eosinophilic cystitis by Brown in 1960,1 6 additional cases have been described in the English literature2- 5 and 17 cases in the foreign literature,. 7 The etiology remains obscure and treatment has been empirical. Herein are reported 3 additional cases of this disease. CASE REPORTS
Case 1. F. F., a 49-year-old white woman, was admitted to Parkland Hospital on November 13, 1969, with gross hematuria 2 days in duration and dysuria, frequency, urgency and nocturia 2 weeks in duration. This had been preceded by 2 years of intermittent lower urinary tract irritative symptoms without chills or fever. The only pertinent physical finding was a firm, midline, non-tender pelvic mass. Hemoglobin was 14 mg. per cent, and the white blood count was 12,500 per cu. mm. with 5 per cent eosinophils. Urinary findings included 4 plus proteinuria with 50 red and 50 white cells per high power field. The initial urine culture was sterile, and the blood urea nitrogen (BUN) and creatinine were normal. An excretory urogram (IVP) demonstrated dilated ureters and calices, and the cystogram revealed a thick-walled, irregular bladder of small capacity without vesicoureteral reflux. On the post-voiding IVP the ureters appeared to be partially obstructed at the ureterovesical junction (fig. 1). Cystoscopic examination revealed that the bladder was diffusely involved with raised plaques 5 to 10 mm. in size which were yellowish and erythematous. Several ulcerated areas were covered with shaggy exudate and the remainder of the mucosa was edematous with bullae formation. Pelvic examination under anesthesia confirmed that the pelvic mass was indeed a thickened bladder. Our impresAccepted for publication December 1970. Read at annual meeting of South Central Section, American Urological Association, Dallas, Texas, October 4-7, 1970. 1 Brown, E. W.: Eosinophilic granuloma of the bladder. J. Urol., 83: 665, 1960. 2 Palubinskas, A. J.: Eosinophilic cystitis: case report of eosinophilic infiltration of urinary bladder. Radiology, 76: 589, 1960. 3 Farber, S. and Vawter, G. F.: Clinical pathological conference. J. Pediat., 62: 941, 1963. 4 Wenzl, J. E., Greene, L. F. and Harris, L. E.: Eosinophilic cystitis. J. Pediat., 64: 746, 1964. 6 Champion, R.H. and Ackles, R. C.: Eosinophilic cystitis. J. Urol., 96: 729, 1966. 6 Perlmutter, A. D., Edlow, J.B. and Kevy, S. V.: Toxocara antibodies in eosinophilic cystitis. J. Pediat., 73: 340, 1968. 7 Zeitlhofer, J. and Bibus, B.: Zur Klinik und Pathologie des eosinophilen Harnblaseninfiltrates. Wien. Klin. Wschr., 79: 958, 1967. 854
sion at this time was a high-grade infiltrating bladder carcinoma. Histological examination of the bladder biopsy surprisingly revealed intact transitional epithelium with a subepithelial dense infiltration of mature eosinophils which were most prominent around vessels (fig. 2). Following cystoscopy, the patient was treated with nitrofurantoin. The symptoms subsided and at cystoscopic examination 3 weeks later marked resolution of the process was noted with only a small area of involvement remaining on the posterior wall. The patient failed to return for followup. Case 2. D. B., a 48-year-old black man, was admitted to Parkland Hospital on October 11, 1969 in a comatose state. History obtained from the family included difficult voiding for 2 weeks prior to hospitalization. The blood pressure was 210/120 mm. Hg, the respiratory rate was 36 per minute. Uremic frost and 1 plus ankle edema were noted on physical examination. The BUN was 230 mg. per cent, creatinine 33.3 mg. per cent, hemoglobin 8.2 gm. per cent and white blood count was 8,500 per cu. mm. Upon insertion of a catheter, 800 cc blood-tinged urine was obtained. Because of the patient's profoundly uremic state he underwent peritoneal dialysis and his condition improved. A cystogram demonstrated a triangular shaped, thick-walled bladder with multiple cellules and cystoscopic examination confirmed the trabeculation. There were no significant mucosa! abnormalities. The bladder neck seemed constricted and bilobar prostatic enlargement was present. The ureters were dilated and tortuous on retrograde pyelography and the calices were slightly blunted. The renal parenchyma appeared normal. Initial urine culture yielded Klebsiella and a cystometrogram was normal. Subsequent hemograms demonstrated persistent eosinophilia from 12 to 20 per cent with a normal white blood count. Serum protein electrophoresis revealed hyperglobulinemia and the serum complement was normal. Stools examined for ova, cysts and parasites were negative. Because of persistent uremia, the patient underwent intermittent peritoneal dialysis for 1 month and concomitant catheter drainage. Interpretation of percutaneous renal biopsies obtained 1 month apart was mild interstitial fibrosis without glomerular abnormalities. The BUN and creatinine stabilized at 55 and 7.5 mg. per cent, respectively. A Y-V plasty of the vesical neck and suprapubic cystostomy were performed. Microscopic examination of a specimen from the bladder neck revealed a subepithelial infiltrate, primarily of eosinophils, and interstitial edema.
EOS1NOPHILIC CYSTITIS
Despite operation, the patient remained unable to void. Three months later he underwent a 10 gm. transurethral resection of the prostate and bladder demonneck. Sections of the bladder neck
FIG. 1. IVP demonstrates biiateral hydronephrosis
and ureterectasis secondary to obstruction at ureterovesical junction from thickened bladder wall.
855
strated the eosinophilic infiltration. A Wright's stain of the urine sediment revealed primarily mono-nuclear and plasma cells. Since he continued to void poorly, an internal urethrotomy was done. In view of the bladder histology, he was placed on 60 mg. prednisolone daily with a resultant excellent urinary stream and a flow of 16 cc per second. The BUN and creatinine remained at about 60 and 7 mg. per cent, respectively. Case S. \V. T., a 53-year-old white man, was admitted to the hospital after 10 weeks of treatment with various antibacterial agents which had failed to relieve severe symptoms of cystitis. The history was remarkable only in that he had been taking coumadin for several years following a myocardial infarction. Physical examination was unremarkable. A urine sample contained 3 to 4 plus albumin and many polymorphonuclear leukocytes were seen on the unstained sediment. Urine culture was sterile. An IVP demonstrated ureteritis cystica and mild ureterectasis bilaterally, and a cystogram demonstrated a small capacity, thick-walled bladder with bilateral vesicoureteral reflux. Cystoscopic exam~ ination revealed a diffuse inflammatory reaction with no obstruction. A subepithelial infiltration of eosinophils was seen on bladder biopsy. He received 30 mg. prednisone daily and tained symptomatic improvement for a short while but the symptoms recurred and he was talized twice for hydrostatic dilatation of the der. Coumadin was discontinued each time he was hospitalized for instrumentation and the subsided, only to recur when he resumed the He is currently doing well on 10 mg. daily. The coumadin was discontinued. REVIEW OF THE LITERATURE AND DISCUSSION
The clinical presentation of this disease mimics the more common forms of cystitis but heavy albumi-
Fm. 2. Bladder biopsy reveals intact transitional epithelium over subepithelial infiltrate of eosinophils and interstitial. edema.
856
GOLDSTEIN
nuria, hematuria and peripheral blood and urinary eosinophilia serve to distinguish it. Cystograms demonstrate a small capacity, thick-walled bladder. IVP commonly reveals obstruction at the ureterovesical junction. Cystoscopic examination presents a striking picture, often resembling infiltrating tumor, with raised pale red to yellow 5 to 10 mm. plaques. Occasional ulcers are seen covered with fibrin and there may be extensive bullous edema of the mucosa. The process has predilection for the posterior wall of the bladder and the areas surrounding the ureteral ostia. Transitional epithelium over a dense infiltration of eosinophils in the subepithelium and superficial muscular layers is the hallmark of the histology, and the eosinophils are usually most predominant around vessels. Frequently there are plasma cells and macrophages in the infiltrate and often there is interstitial edema. Of the 7 cases reported in the English literature, 5 were in children. 3- 6 The urine culture was initially sterile in one of these, 4 as it was in 2 of our cases. However, in the other cases, culture yielded a variety of the common urinary tract pathogens. No ova or parasites have been demonstrated in the urine, stool or tissue, although 1 patient had serum antibodies to Toxocara cati. 6 The serum of 2 of our patients was tested for antibodies to this parasite and both had negative titers. In 2 patients an ovarian teratoma was discovered subsequently but the significance of this is unclear. The clinical course of the disease is extremely unpredictable, varying from about 2 weeks to 6 months or more. There is a tendency to chronicity with exacerbations. Zeitlhofer and Bibus found 17 cases of eosinophilic cystitis between 1960 and 1967 in the course of examining 1,000 bladder biopsies done for suspected tumor.7 Six patients had no previous history of urological disease while 4 patients had coexisting urinary tract disease such as stones, epididymitis and hypernephroma in 1 case. Seven cases were diagnosed on transurethral resection of what appeared to be a recurrent bladder tumor in patients who had 1 or more bladder carcinomas resected. There are numerous reports in the literature of eosinophilic gastroenteritis,8 and the diffuse type has the same gross and microscopic appearance as eosinophilic cystitis. About half of these patients had histories of allergy and it is noteworthy that 1 patient with eosinophilic gastroenteritis also had eosinophilic cystitis. The literature on urinary tract allergy is sparse, and allergy is considered a rare cause of urologic symptoms. However, those investigators interested in allergic urinary tract disease believe that it is not a clinical rarity. Hypersensitivity reactions can 8 Marymont, J. H., Jr. and Crumpacker, L. K.: Eosinophilic gastroenteritis with small bowel obstruction. J. Kansas Med. Soc., 68: 222, 1967.
affect any part of the urinary tract, and there are numerous well-documented reports ol' renal colic, symptoms of irritable bladder, hematuria and pyuria secondary to the ingestion of a variety of foods and drugs. 9- 12 Incriminated in producing urinary tract allergic reactions is a long list of foods, inhalants and medications, including alcohol. There is also good reason to suspect that contact allergens such as condoms, vaginal tampons, spermatocidal jellies and even sensitization to micro-organisms cause a number of cases of cystitis and urethritis. Pastinszky believes this is the most common route of sensitization of the bladder and urethra.13 Powell demonstrated clinically and histologically an allergic etiology in 5 per cent of 114 female patients with bladder complaints. Kindall and Nickels believe hypersensitivity causes many cases of the urethro-trigonitis syndrome in women. 11 Eosinophils may be found in the urethral discharge of 30 per cent of patients with non-gonococcal urethritis, which suggests an allergic etiology. 13 It seems apparent that urinary tract allergy is not diagnosed more often because it is not considered. CONCLUSION
Kindall and Nickels, Pastinszky and others have described the gross and microscopic pathology seen in eosinophilic cystitis and have shown good evidence for an allergic etiology.11 • 13 These cases were associated with monocytes and eosinophils in the urine and frequently eosinophilia of the blood. Failure to uncover the offending allergen in the reported cases of eosinophilic cystitis undoubtedly means that the search was not intensive enough. In our third case coumadin was strongly suspected. It would appear that eosinophilic cystitis is only a more severe form of vesical allergy. A Wright's stain of the urine sediment and a differential peripheral white blood count s\lould be obtained in every case of chronic or recurrent cystitis in which the usual causes have been eliminated by thorough investigation of the urinary tract. If either of these reveals eosinophilia or the urinary sediment contains plasma cells and monocytes, a biopsy of the bladder should be done to confirm the diagnosis of vesical allergy, even though there are minimal mucosal abnormalities. In the more severe form of the disease, the biopsy will differentiate allergic cystitis from neoplasm. Therapy should be directed toward identifying 9 Unger, D. L., Kubik, F. and Unger, L.: Urinary tract allergy. J.A.M.A., 170: 1308, 1959. 10 Eisenstaedt, J. S.: Allergy and drug hypersensitivity of the urinary tract. J. Urol., 66: 154, 1951. 11 Kindall, L. and Nickels, T. T.: Allergy of the pelvic urinary tract in the female: a preliminary report. J. Urol., 61: 222, 1949. 12 Walter, C. K.: Allergy as cause of genitourinary symptoms: clinical considerations. Ann. Allergy, 16: 158, 1958. 13 Pastinszky, I.: The allergic diseases of the male genitourinary tract with special reference to allergic urethritis and cystitis. Urol. Int., 9: 288, 1959.
EOSINOPHILIC CYSTITIS
J
the offending allergen if possible. An allergist should be consulted in cases in which the allergen is not apparent or desensitization is necessary. If the urine is infected, the appropriate antibiotics should be used to combat the common occurrence of secondary bacterial infection. Antihistamines may be tried in the milder cases but if symptoms are severe, a short course of corticosteroids may be indicated. The urologist should carefully follow these patients as the coexistence of other urinary tract disease is common, especially with the more severe form of the disease. If symptoms recur cystoscopic examination and IVPs should be repeated. SUMMARY
Twenty-seven cases of eosinophilic cystitis have appeared in the literature, including the 3 cases reported herein. The presenting symptoms are the same as those in the more common forms of cystitis but there is a tendency to chronicity with exacerba-
857
tions. The disease may be suspected by heavy proteinuria and eosinophilia of the urine and blood. Frequently a thick-walled, small capacity bladder with obstruction at the ureterovesical junction is seen on IVP and cystoscopic examination presents a striking picture often resembling tumor. Histologically, the vesical subepithelial layers are invaded by dense infiltration of eosinophils. There is convincing evidence that urinary tract allergy is not a medical rarity but that its milder forms may be quite common. Vesical hypersensitivity reactions may be induced by a variety of antigenic substances and the most severe manifestation of vesical allergy is eosinophilic cystitis. The diagnosis of vesical allergy must be confirmed by bladder biopsy. Treatment usually consists of antibiotics for secondary bacterial infection, corticosteroids if symptoms are severe and identification and removal of the offending allergen from the patient's environment.
THE JOURNAL OF UROLOGY
Copyright
© 1971 by The Williams
& Wilkins Co.
EOSINOPHILIC CYSTITIS MICHAEL GOLDSTEIN From the Department of Urology, University of Texas Southwestern Medical School, Dallas, Texas
Since the first case report of eosinophilic cystitis by Brown in 1960,1 6 additional cases have been described in the English literature2- 5 and 17 cases in the foreign literature,. 7 The etiology remains obscure and treatment has been empirical. Herein are reported 3 additional cases of this disease. CASE REPORTS
Case 1. F. F., a 49-year-old white woman, was admitted to Parkland Hospital on November 13, 1969, with gross hematuria 2 days in duration and dysuria, frequency, urgency and nocturia 2 weeks in duration. This had been preceded by 2 years of intermittent lower urinary tract irritative symptoms without chills or fever. The only pertinent physical finding was a firm, midline, non-tender pelvic mass. Hemoglobin was 14 mg. per cent, and the white blood count was 12,500 per cu. mm. with 5 per cent eosinophils. Urinary findings included 4 plus proteinuria with 50 red and 50 white cells per high power field. The initial urine culture was sterile, and the blood urea nitrogen (BUN) and creatinine were normal. An excretory urogram (IVP) demonstrated dilated ureters and calices, and the cystogram revealed a thick-walled, irregular bladder of small capacity without vesicoureteral reflux. On the post-voiding IVP the ureters appeared to be partially obstructed at the ureterovesical junction (fig. 1). Cystoscopic examination revealed that the bladder was diffusely involved with raised plaques 5 to 10 mm. in size which were yellowish and erythematous. Several ulcerated areas were covered with shaggy exudate and the remainder of the mucosa was edematous with bullae formation. Pelvic examination under anesthesia confirmed that the pelvic mass was indeed a thickened bladder. Our impresAccepted for publication December 1970. Read at annual meeting of South Central Section, American Urological Association, Dallas, Texas, October 4-7, 1970. 1 Brown, E. W.: Eosinophilic granuloma of the bladder. J. Urol., 83: 665, 1960. 2 Palubinskas, A. J.: Eosinophilic cystitis: case report of eosinophilic infiltration of urinary bladder. Radiology, 76: 589, 1960. 3 Farber, S. and Vawter, G. F.: Clinical pathological conference. J. Pediat., 62: 941, 1963. 4 Wenzl, J. E., Greene, L. F. and Harris, L. E.: Eosinophilic cystitis. J. Pediat., 64: 746, 1964. 6 Champion, R.H. and Ackles, R. C.: Eosinophilic cystitis. J. Urol., 96: 729, 1966. 6 Perlmutter, A. D., Edlow, J.B. and Kevy, S. V.: Toxocara antibodies in eosinophilic cystitis. J. Pediat., 73: 340, 1968. 7 Zeitlhofer, J. and Bibus, B.: Zur Klinik und Pathologie des eosinophilen Harnblaseninfiltrates. Wien. Klin. Wschr., 79: 958, 1967. 854
sion at this time was a high-grade infiltrating bladder carcinoma. Histological examination of the bladder biopsy surprisingly revealed intact transitional epithelium with a subepithelial dense infiltration of mature eosinophils which were most prominent around vessels (fig. 2). Following cystoscopy, the patient was treated with nitrofurantoin. The symptoms subsided and at cystoscopic examination 3 weeks later marked resolution of the process was noted with only a small area of involvement remaining on the posterior wall. The patient failed to return for followup. Case 2. D. B., a 48-year-old black man, was admitted to Parkland Hospital on October 11, 1969 in a comatose state. History obtained from the family included difficult voiding for 2 weeks prior to hospitalization. The blood pressure was 210/120 mm. Hg, the respiratory rate was 36 per minute. Uremic frost and 1 plus ankle edema were noted on physical examination. The BUN was 230 mg. per cent, creatinine 33.3 mg. per cent, hemoglobin 8.2 gm. per cent and white blood count was 8,500 per cu. mm. Upon insertion of a catheter, 800 cc blood-tinged urine was obtained. Because of the patient's profoundly uremic state he underwent peritoneal dialysis and his condition improved. A cystogram demonstrated a triangular shaped, thick-walled bladder with multiple cellules and cystoscopic examination confirmed the trabeculation. There were no significant mucosa! abnormalities. The bladder neck seemed constricted and bilobar prostatic enlargement was present. The ureters were dilated and tortuous on retrograde pyelography and the calices were slightly blunted. The renal parenchyma appeared normal. Initial urine culture yielded Klebsiella and a cystometrogram was normal. Subsequent hemograms demonstrated persistent eosinophilia from 12 to 20 per cent with a normal white blood count. Serum protein electrophoresis revealed hyperglobulinemia and the serum complement was normal. Stools examined for ova, cysts and parasites were negative. Because of persistent uremia, the patient underwent intermittent peritoneal dialysis for 1 month and concomitant catheter drainage. Interpretation of percutaneous renal biopsies obtained 1 month apart was mild interstitial fibrosis without glomerular abnormalities. The BUN and creatinine stabilized at 55 and 7.5 mg. per cent, respectively. A Y-V plasty of the vesical neck and suprapubic cystostomy were performed. Microscopic examination of a specimen from the bladder neck revealed a subepithelial infiltrate, primarily of eosinophils, and interstitial edema.
EOS1NOPHILIC CYSTITIS
Despite operation, the patient remained unable to void. Three months later he underwent a 10 gm. transurethral resection of the prostate and bladder demonneck. Sections of the bladder neck
FIG. 1. IVP demonstrates biiateral hydronephrosis
and ureterectasis secondary to obstruction at ureterovesical junction from thickened bladder wall.
855
strated the eosinophilic infiltration. A Wright's stain of the urine sediment revealed primarily mono-nuclear and plasma cells. Since he continued to void poorly, an internal urethrotomy was done. In view of the bladder histology, he was placed on 60 mg. prednisolone daily with a resultant excellent urinary stream and a flow of 16 cc per second. The BUN and creatinine remained at about 60 and 7 mg. per cent, respectively. Case S. \V. T., a 53-year-old white man, was admitted to the hospital after 10 weeks of treatment with various antibacterial agents which had failed to relieve severe symptoms of cystitis. The history was remarkable only in that he had been taking coumadin for several years following a myocardial infarction. Physical examination was unremarkable. A urine sample contained 3 to 4 plus albumin and many polymorphonuclear leukocytes were seen on the unstained sediment. Urine culture was sterile. An IVP demonstrated ureteritis cystica and mild ureterectasis bilaterally, and a cystogram demonstrated a small capacity, thick-walled bladder with bilateral vesicoureteral reflux. Cystoscopic exam~ ination revealed a diffuse inflammatory reaction with no obstruction. A subepithelial infiltration of eosinophils was seen on bladder biopsy. He received 30 mg. prednisone daily and tained symptomatic improvement for a short while but the symptoms recurred and he was talized twice for hydrostatic dilatation of the der. Coumadin was discontinued each time he was hospitalized for instrumentation and the subsided, only to recur when he resumed the He is currently doing well on 10 mg. daily. The coumadin was discontinued. REVIEW OF THE LITERATURE AND DISCUSSION
The clinical presentation of this disease mimics the more common forms of cystitis but heavy albumi-
Fm. 2. Bladder biopsy reveals intact transitional epithelium over subepithelial infiltrate of eosinophils and interstitial. edema.
856
GOLDSTEIN
nuria, hematuria and peripheral blood and urinary eosinophilia serve to distinguish it. Cystograms demonstrate a small capacity, thick-walled bladder. IVP commonly reveals obstruction at the ureterovesical junction. Cystoscopic examination presents a striking picture, often resembling infiltrating tumor, with raised pale red to yellow 5 to 10 mm. plaques. Occasional ulcers are seen covered with fibrin and there may be extensive bullous edema of the mucosa. The process has predilection for the posterior wall of the bladder and the areas surrounding the ureteral ostia. Transitional epithelium over a dense infiltration of eosinophils in the subepithelium and superficial muscular layers is the hallmark of the histology, and the eosinophils are usually most predominant around vessels. Frequently there are plasma cells and macrophages in the infiltrate and often there is interstitial edema. Of the 7 cases reported in the English literature, 5 were in children. 3- 6 The urine culture was initially sterile in one of these, 4 as it was in 2 of our cases. However, in the other cases, culture yielded a variety of the common urinary tract pathogens. No ova or parasites have been demonstrated in the urine, stool or tissue, although 1 patient had serum antibodies to Toxocara cati. 6 The serum of 2 of our patients was tested for antibodies to this parasite and both had negative titers. In 2 patients an ovarian teratoma was discovered subsequently but the significance of this is unclear. The clinical course of the disease is extremely unpredictable, varying from about 2 weeks to 6 months or more. There is a tendency to chronicity with exacerbations. Zeitlhofer and Bibus found 17 cases of eosinophilic cystitis between 1960 and 1967 in the course of examining 1,000 bladder biopsies done for suspected tumor.7 Six patients had no previous history of urological disease while 4 patients had coexisting urinary tract disease such as stones, epididymitis and hypernephroma in 1 case. Seven cases were diagnosed on transurethral resection of what appeared to be a recurrent bladder tumor in patients who had 1 or more bladder carcinomas resected. There are numerous reports in the literature of eosinophilic gastroenteritis,8 and the diffuse type has the same gross and microscopic appearance as eosinophilic cystitis. About half of these patients had histories of allergy and it is noteworthy that 1 patient with eosinophilic gastroenteritis also had eosinophilic cystitis. The literature on urinary tract allergy is sparse, and allergy is considered a rare cause of urologic symptoms. However, those investigators interested in allergic urinary tract disease believe that it is not a clinical rarity. Hypersensitivity reactions can 8 Marymont, J. H., Jr. and Crumpacker, L. K.: Eosinophilic gastroenteritis with small bowel obstruction. J. Kansas Med. Soc., 68: 222, 1967.
affect any part of the urinary tract, and there are numerous well-documented reports ol' renal colic, symptoms of irritable bladder, hematuria and pyuria secondary to the ingestion of a variety of foods and drugs. 9- 12 Incriminated in producing urinary tract allergic reactions is a long list of foods, inhalants and medications, including alcohol. There is also good reason to suspect that contact allergens such as condoms, vaginal tampons, spermatocidal jellies and even sensitization to micro-organisms cause a number of cases of cystitis and urethritis. Pastinszky believes this is the most common route of sensitization of the bladder and urethra.13 Powell demonstrated clinically and histologically an allergic etiology in 5 per cent of 114 female patients with bladder complaints. Kindall and Nickels believe hypersensitivity causes many cases of the urethro-trigonitis syndrome in women. 11 Eosinophils may be found in the urethral discharge of 30 per cent of patients with non-gonococcal urethritis, which suggests an allergic etiology. 13 It seems apparent that urinary tract allergy is not diagnosed more often because it is not considered. CONCLUSION
Kindall and Nickels, Pastinszky and others have described the gross and microscopic pathology seen in eosinophilic cystitis and have shown good evidence for an allergic etiology.11 • 13 These cases were associated with monocytes and eosinophils in the urine and frequently eosinophilia of the blood. Failure to uncover the offending allergen in the reported cases of eosinophilic cystitis undoubtedly means that the search was not intensive enough. In our third case coumadin was strongly suspected. It would appear that eosinophilic cystitis is only a more severe form of vesical allergy. A Wright's stain of the urine sediment and a differential peripheral white blood count s\lould be obtained in every case of chronic or recurrent cystitis in which the usual causes have been eliminated by thorough investigation of the urinary tract. If either of these reveals eosinophilia or the urinary sediment contains plasma cells and monocytes, a biopsy of the bladder should be done to confirm the diagnosis of vesical allergy, even though there are minimal mucosal abnormalities. In the more severe form of the disease, the biopsy will differentiate allergic cystitis from neoplasm. Therapy should be directed toward identifying 9 Unger, D. L., Kubik, F. and Unger, L.: Urinary tract allergy. J.A.M.A., 170: 1308, 1959. 10 Eisenstaedt, J. S.: Allergy and drug hypersensitivity of the urinary tract. J. Urol., 66: 154, 1951. 11 Kindall, L. and Nickels, T. T.: Allergy of the pelvic urinary tract in the female: a preliminary report. J. Urol., 61: 222, 1949. 12 Walter, C. K.: Allergy as cause of genitourinary symptoms: clinical considerations. Ann. Allergy, 16: 158, 1958. 13 Pastinszky, I.: The allergic diseases of the male genitourinary tract with special reference to allergic urethritis and cystitis. Urol. Int., 9: 288, 1959.
EOSINOPHILIC CYSTITIS
J
the offending allergen if possible. An allergist should be consulted in cases in which the allergen is not apparent or desensitization is necessary. If the urine is infected, the appropriate antibiotics should be used to combat the common occurrence of secondary bacterial infection. Antihistamines may be tried in the milder cases but if symptoms are severe, a short course of corticosteroids may be indicated. The urologist should carefully follow these patients as the coexistence of other urinary tract disease is common, especially with the more severe form of the disease. If symptoms recur cystoscopic examination and IVPs should be repeated. SUMMARY
Twenty-seven cases of eosinophilic cystitis have appeared in the literature, including the 3 cases reported herein. The presenting symptoms are the same as those in the more common forms of cystitis but there is a tendency to chronicity with exacerba-
857
tions. The disease may be suspected by heavy proteinuria and eosinophilia of the urine and blood. Frequently a thick-walled, small capacity bladder with obstruction at the ureterovesical junction is seen on IVP and cystoscopic examination presents a striking picture often resembling tumor. Histologically, the vesical subepithelial layers are invaded by dense infiltration of eosinophils. There is convincing evidence that urinary tract allergy is not a medical rarity but that its milder forms may be quite common. Vesical hypersensitivity reactions may be induced by a variety of antigenic substances and the most severe manifestation of vesical allergy is eosinophilic cystitis. The diagnosis of vesical allergy must be confirmed by bladder biopsy. Treatment usually consists of antibiotics for secondary bacterial infection, corticosteroids if symptoms are severe and identification and removal of the offending allergen from the patient's environment.