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Acute Exudative Cystitis of Undetermined Etiology1
ACUTE EXUDATIVE CYSTITIS OF UNDETERMINED ETIOLOGY 1 J. V. BERRY
AND
N. E. BERRY
The purpose of this communication is to call attention to the importance of a more general knowledge of the pyurias of unknown etiology variously described as acute exudative cystitis, acute interstitial cystitis, acute hemorrhagic cystitis, amicrobic pyuria and Reiter's disease. Papers have appeared on the subject by Cook, Moore, Colby, Briggs, Sargent, and others, but there are an appreciable number of urologists who have never recognized a case. Many medical officers attached to urological services can recall having seen cases that probably belonged to this group which were not recognized as such because the officers were not familiar with the syndrome. The characteristic feature of the condition is a history of non-specific urethritis of variable duration, followed by an acute hemorrhagic cystitis. The acute onset of frequency and strangury, the profuse hematuria and the absence of loin pain and febrile reaction characterize this syndrome from most other infections of the urinary tract. Admittedly the cystitis is only part of the picture, but it is a most distressing one and considering its protracted course, if not recognized may become a serious debilitating disease. In Reiter's syndrome, conjunctivitis and arthritis are also present. It might be argued that this syndrome is a separate entity, but it has so much in common with the other group of cases that they may properly be discussed together. They all have non-specific urethritis, intense cystitis and sterile urine. Further, they all show dilatation of the upper urinary tract. Reiter observed the syndrome in a young German officer in 1916. Following an acute gastro-intestinal upset the man had a purulent urethral discharge, which was accompanied by an acute conjunctivitis and acute arthritis of the right knee. No gonococci could be demonstrated in the urethral or conjunctival discharges. Three weeks after the onset there was an extension of the arthritis to other joints with an acute febrile reaction. After 2 months of the illness had passed the patient had acute cystitis and recurrent conjunctivitis. Since Reiter's original publication some 65 cases have been reported (Miller and McIntyre). Lever and Crawford reviewed the first 45 case records and concluded that in some the syndrome was not complete and in others the bacteriological studies were not rnfficient to exclude the presence of gonococcic infection. These authors commented that nearly half of the cases were soldiers on active duty in either the first or second ·world Wars and that only 1 case had been reported in America. Rosenblum and Sargent have each published a series in the past year. They point out that where all the symptoms are not present, the disease may be mistaken for acute prostatitis, acute cystitis and conjunctivitis. Colby has drawn attention to the upper urinary tract complications in Reiter's disease, and we had a similar case in our series. 1 Read at annual meeting, Western New York-Ontario Urological Society, Thousand Islands Club, September 11-14, 1946. 260
ACUTE EXUDATIVE CYSTITIS
261
Our experience consists pf 24 cases, almost all of them soldiers. They all, had urethritis and all showed the cystoscopic features noted by Hess and Cook. Three cases had sever~, polyartimµar arthritis, 4 cases had acute bilateral conjunctivitis, while 1 had acute iritis as the only complication of the urinary tract lesion. In 1 case the purpuric vesicular dermatitis, described by Lever and Crawford, developed. Of those whose upper urinary tracts were investigated, all showed dilatation: some very marked and with recovery this ordinarily, but not always, rapidly improved. CASE REPORTS
Case 1. A 30 year old married soldier, Private S. L., had no history of any illness prior to enlistment in April 1943. About June 7, 1944, an acute creamy urethral discharge developed which was negative for gonococci. Extramarital sexual contact was denied. There was no improvement after a 5 day course of sulfathiazole, and 2 days later bilateral purulent conjunctivitis developed. This improved rapidly tinder treatment with sulfathiazole ointment but 2 weeks later he had an acutely swollen and painful left knee joint, followed by similar involvement of the right knee. He was admitted to a military hospital June 23, 1944, and given sulfadiazene therapy. There was still no improvement in either the discharge or the arthritis and on July 1 he had actl.te pain and swelling of the small joints of both hands. The successive joint reactions had caused a gradual febrile response and by July 15 the patient was acutely ill with fever of 102°. The sedimentation rate showed a marked rise from 11 to 103 mm. and leucocyte count to 20,000. Cultures of urine and joint fluid failed to reveal any organisms. The urinary symptoms had continued with such severity that a cystoscope was passed on August 8, 1944. The bladder capacity wlls about an ounce and distention caused bleeding. The mucosa was intensely inflamed and heaped up with an edematous reaction of the whole bladder surface. An exudate covered the walls like a spider web. There was no evidence of any necrotic tissue present. Bladder irrigations were performed on frequent occa:oions using silver nitrate solutions and argyrol. Penicillin was given to the extent of 600,000 units. All of these drugs gave little -relief. Intravenous urograms revealed a dilatation 0f the upper tract and a very much contracted bladder (fig. 1). N ovarsenobenzol was given in small doses 3 times a week, and after the first week of treatment the bladder symptoms began to clear. The arthritis improved, but not until a suppurative focus in the tonsils was discovered and subsequently removed did the patient obtain much symptomatic relief. He was out of bed on October 15 and discharged from the hospital 2 weeks later. We were able to trace this man after a year's absence and discovered he had a recurrence of conjunctivitis and cystitis of mild duration. There was no recurrence of arthritis. Case 2. This 25 year old soldier, Private J. N., reported an acute urethral
262
J. V. BERRY AND N. E. BERRY
discharge to his medical officer in March 1944. A clinical diagnosis of gonorrhoea was made, although there were no typical gonococci reported in the smears. Treatment with sulfathiazole for 5 days brought about cessation of discharge and he was apparently cured. Two weeks later he was admitted to a military hospital with a purpuric vesicular dermatitis and treated first with lead lotion and then with sulfathiazole ointment. The dermatitis was improved slightly but not cured. About 1 week after admission to the hospital he began to complain of dysuria and frequency of urination with terminal hematuria. Rectal examination showed
Fm. 1. Case 1. Contracted bladder with dilated upper urinary·, tract
a tender and boggy prostate but no appreciable enlargement. Hot sitz baths and diathermy were advised with all urinary symptoms becoming aggravated. On June 7, 1944, cystoscopy showed that the bladder was intolerant to more than 2 ounces of fluid. There was intensely acute cystitis with a great deal of adherent exudate. The prostatic urethra, apart from acute congestion, presented no evidence of abscess. The ureteral orifices were not identi'fied because of the marked edema of the trigone. Throughout this period the dermatitis showed numerous exacerbations and remissions, but at not time did it completely disappear. It was confined mainly to the hands and feet, both dorsal and ventral surfaces being affected, the back of the neck and the shoulder regions. During the latter part of July he had pain and swelling of both hands and feet with a low grade fever, and he began to decline markedly in health. There was a loss of 30 pounds in weight and[hc
ACUTE EXUDATIVE CYSTITIS
263
showed a marked degree of anemia. Frequency of urination and strangury had become intolerable with gross hematuria. Intravenous urograms showed marked dilatation of both lower ureters and an appreciable dilatation of both renal pelves. He continued to suffer a good deal; increasing pain in the hands and feet developed, and the left knee and right elbow became involved. This was accompanied by an exacerbation of fever to 101 °. On September 1, 1944, he was started on a course of N ovarsenobenzol 0.3 gm. and this was repeated 4 days later. Definite improvement followed and his temperature fell to normal. Penicillin was now available and a course of 200,000 units was given with further improvement and he became progressively better. By October 1 his joints and his bladder were virtually normal. This was confirmed by cystoscopy and ureteral catheterization was carried out without obstruction. Pyelograms showed now only a slight dilatation on both sides. Case 3. A 24 year old, married, Air Force Sergeant, S. T., with 4 years' military service in Canada, reported a purulent urethral discharge to his medical officer on July 1, 1945. There was no history of exposure and the urethritis was reported as non-specific. After 3 weeks' sulfa therapy the discharge became gradually worse and he was admitted to a military hospital for further investigation. On admission to hospital he began to complain of some frequency of urination which rapidly became worse and on July 30 cystoscopy was reported as showing marked cystitis with edema and swelling of the posterior urethra and bladder neck. Bacteriological examination of the urine showed sterile pyuria. Following the examination he experienced acute pain with frequency every 5 minutes and hematuria so gross that clots retarded the act of urination. The symptoms appeared to improve somewhat in the first course of 900,000 units of penicillin. The relief of symptoms was soon followed by a severe relapse and despite the use of penicillin and sulfa therapy the patient experienced a 3 weeks' period of excruciating pain and frequency. For the next 3 months the symptoms were almost static with intervals of relief from hematuria and strangury, but with frequency of no less than ½hourly intervals. During the first week in November acute bilateral epididymitis developed. On his admission to the London Military Hospital on December 3, 1945, he appeared quite undernourished and pale with considerable loss of weight but not acutely ill. Cystoscopic examination was performed the next day under pentothal anesthesia. A stricture, which barely permitted a 16 F. cystoscope, was detected in the perineal urethra. The bladder capacity was 1½ounces and the bladder mucosa presented patchy areas of acute inflammation with numerous hemorrhagic areas about the floor and neck of the bladder. The ureteral orifices were swollen and would only admit a, 4 F. bougie with difficulty. The orifices were dilated and catheters were passed which revealed clear urine but bilateral hydronephroses (fig. 2, A). December 11, 1945, 0.3 gm. Novarsenobenzol was given for 3 consecutive days with complete relief of hematuria and relief of frequency for 2 hour inter-
264
J. V. BERRY AND N. E. BERRY
vals. After 6 injections the patient took his 2 weeks' Christmas leave and returned with aggravation of symptoms and occasional hematuria. Cystoscopy was repeated, and on this examination the flame-like hemorrhages had disappeared. Over the same areas of the bladder, small blood cysts appeared which on pathological section proved to be hemangiomata. On February 1 (one month later) the hemangiomata had disappeared, leaving numerous small bleeding ulcers with bright hemorrhagic margins. By the end of February 1946, the patient had received a total of 14 injections of N ovarsenobenzol, with relief of his bladder symptoms but with i,ome microscopic hematuria. On March 15, the bladder capacity had reached 3 ounces.
Frn. 2. Case 3. A, Dilated upper urinary tract.
B, After treatment
There were a few small ulcers about the trigone and ureteral orifices appeared q_uite normal; considerable dilatation of the upper tract however remained. Although this man has recovered from the acute bladder lesion, he has written to me recently to state that his doctor is still giving him periodic dilatations of -the bladder. The last intravenous urogram taken on June 12 showed the lleft renal pelvis normal in size and contour but the right side still showed a mild degree of dilatation (fig. 2, B). ETIOLOGY
The cause of the condition is unknown. A filterable virus has been suggested. It has also been thought to be due to focal infection with toxine in the urine
ACUTE EXUDATIVE CYRTTTTR
265
provoking the reaction or that it may be due to a deep-seated coccal infection in the renal parenchyma. It seems to us significant that in all onr cases therewas antecedent urethritis and, with one exception, this was non-specific. Admittedly, we know little about the cause of non-specific urethritis but there is the possibility that it may be specific, the o"ganism not yet being identified. The consistently negative smears and cultures in a condition which is obviously inflammatory can lead only to this conclusion. DIAGNOSIS
The differential diagnosis concerns the exclusion, first, of gonorrhoeal urethritis and prostatitis, and secondly, tuberculosis. The clinical picture and bladder appearances are highly suggestive of renal tuberculosis. The sterile
mil
Frn. 3. Contracted bladder with dilated upper tract with whole process reversed in 17 days after institution of specific treatment.
urine adds to the evidence. A diagnosis of tuberculosis should not be made without proof of the presence of tubercle bacilli. One is apt to linger too long under the impression that these cases may be prostatitis, the prostate being exquisitely tender and often presenting a boggy sensation. This is, however, due to the intense cystitis and ,Yhen properly treated there is not usually any residual prostatic infection. Carcinoma of a diffusely infiltrating type might be a problem to differentiate, but should not be difficult. Familiarity with the syndrome makes the diagnosis obvious. The finding on x-ray of a contracted bladder with dilated ureters and renal pelves is very suggestive of this condition. Characteristically this whole process can be reversed in a short period of time with specific treatment and we believe that such an observation is diagnostic of the disease (fig. 3).
266
J. V. BERRY AND N. E. BERRY
PATHOLOGY
Hess was one of the first to contribute any pathological information on the lesion of acute hemorrhagic cystitis. The early lesion is hemorrhage with mild inflammation of the mucosal stroma. Later vascular channels form in the hemorrhagic areas and finally develop to form hemangiomata. In the terminal stage the mucosa lining the hemangiomata breaks down due to thrombosis, the result of inflammation and scarring, with the formation of punctate ulcers which may appear necrotic but which usually present a hemorrhagic margin. Peters has compared these pathological changes in the bladder typical -0f the clinical entity known as Hun:iier's ulcer. Since no organisms could be demonstrated in the urine, sections of tissue from the bladder were macerated and spread on culture media with negative results. Smears of urethrrl and conjunctival discharges and joint effusions yielded negative findings. The blood picture was typically secondary hypo-chromic anemia. The leucocyte response and sedimentation rate was noted to rise and fall in relation to the acuteness of the joint lesions. Apart from'some ,coincidental findings, the laboratory data were of little interest in the1whole :series. TREATMENT
The treatment is simplified by correct and early diagnosis, though not all the patients tend to respond in the same way. Local treatment of many kinds has been tried by intermittent and' continuous bladder drainage but all were limited by the highly sensitive and intolerant bladders. Mandelic acid and sulfonamides were of little value. Penicillin has not been generally effective but seemed definitely of value in one of our cases. N eoarsphenamine in small
A series of 24 cases of acute exudative cystitis is presented, 3 in detail. A :few cases were complicated by arthritis, .conjunctivitis, iritis and dermatitis. The acute vesical syndrome is characterized by a profuse abacterial pyuria :and gross hematuria. The end result of the inflammatory lesion is a contracted :and ulcerated bladder with terminal ureteritis and marked dilatation of the upper urinary tract. We believe that the condition is caused by an organism, possibly a spirochete :and has some relation to non-specific urethritis. Differential diagnosis concerns the exclusion of gonorrhoea, tuberculosis and malignancy. Familiarity with the symptoms and the urographic findings makes the diagnosis simple. Characteristically the whole picture can be reversed in a short period of time
ACUTE EXUDA'l'IVE CYSTITIS
with specific treatment, the neoarsphenamines being usually employed. harsen, in our experience, is equally efficacious.
Medical Arts Bldg., Ottawa, Canada (J.V.B.) Kingston, Ontario, Canada (:N.E.B.) REFERENCES BRIGGS, W. I.: J. Urol., 34: 230, 1935. COLBY, F. H.: J. Urol., 52: 415, 1944. -CooK, E. N.: Proc. Staff Meet. Mayo Clinic, 19: 377, 1944. HEss, E.: Personal communication. LEVER, W. F. AND CRAWFORD, G. M.: Arch. Dermat. & Syphil., 49: 389, 1944. MILLER, C. D. AND McINTYRE, D. W.: Ann. Int. Med., 23: 673, 1945. MooRE, T.: J. Urol., 49: 203, 1943. PETERS, D. 0.: Brit. Med. J., 1: 160, 1946. SARGENT, J.C.: J. Urol., 54: 556, 1945.
267
Map-
AND
N. E. BERRY
The purpose of this communication is to call attention to the importance of a more general knowledge of the pyurias of unknown etiology variously described as acute exudative cystitis, acute interstitial cystitis, acute hemorrhagic cystitis, amicrobic pyuria and Reiter's disease. Papers have appeared on the subject by Cook, Moore, Colby, Briggs, Sargent, and others, but there are an appreciable number of urologists who have never recognized a case. Many medical officers attached to urological services can recall having seen cases that probably belonged to this group which were not recognized as such because the officers were not familiar with the syndrome. The characteristic feature of the condition is a history of non-specific urethritis of variable duration, followed by an acute hemorrhagic cystitis. The acute onset of frequency and strangury, the profuse hematuria and the absence of loin pain and febrile reaction characterize this syndrome from most other infections of the urinary tract. Admittedly the cystitis is only part of the picture, but it is a most distressing one and considering its protracted course, if not recognized may become a serious debilitating disease. In Reiter's syndrome, conjunctivitis and arthritis are also present. It might be argued that this syndrome is a separate entity, but it has so much in common with the other group of cases that they may properly be discussed together. They all have non-specific urethritis, intense cystitis and sterile urine. Further, they all show dilatation of the upper urinary tract. Reiter observed the syndrome in a young German officer in 1916. Following an acute gastro-intestinal upset the man had a purulent urethral discharge, which was accompanied by an acute conjunctivitis and acute arthritis of the right knee. No gonococci could be demonstrated in the urethral or conjunctival discharges. Three weeks after the onset there was an extension of the arthritis to other joints with an acute febrile reaction. After 2 months of the illness had passed the patient had acute cystitis and recurrent conjunctivitis. Since Reiter's original publication some 65 cases have been reported (Miller and McIntyre). Lever and Crawford reviewed the first 45 case records and concluded that in some the syndrome was not complete and in others the bacteriological studies were not rnfficient to exclude the presence of gonococcic infection. These authors commented that nearly half of the cases were soldiers on active duty in either the first or second ·world Wars and that only 1 case had been reported in America. Rosenblum and Sargent have each published a series in the past year. They point out that where all the symptoms are not present, the disease may be mistaken for acute prostatitis, acute cystitis and conjunctivitis. Colby has drawn attention to the upper urinary tract complications in Reiter's disease, and we had a similar case in our series. 1 Read at annual meeting, Western New York-Ontario Urological Society, Thousand Islands Club, September 11-14, 1946. 260
ACUTE EXUDATIVE CYSTITIS
261
Our experience consists pf 24 cases, almost all of them soldiers. They all, had urethritis and all showed the cystoscopic features noted by Hess and Cook. Three cases had sever~, polyartimµar arthritis, 4 cases had acute bilateral conjunctivitis, while 1 had acute iritis as the only complication of the urinary tract lesion. In 1 case the purpuric vesicular dermatitis, described by Lever and Crawford, developed. Of those whose upper urinary tracts were investigated, all showed dilatation: some very marked and with recovery this ordinarily, but not always, rapidly improved. CASE REPORTS
Case 1. A 30 year old married soldier, Private S. L., had no history of any illness prior to enlistment in April 1943. About June 7, 1944, an acute creamy urethral discharge developed which was negative for gonococci. Extramarital sexual contact was denied. There was no improvement after a 5 day course of sulfathiazole, and 2 days later bilateral purulent conjunctivitis developed. This improved rapidly tinder treatment with sulfathiazole ointment but 2 weeks later he had an acutely swollen and painful left knee joint, followed by similar involvement of the right knee. He was admitted to a military hospital June 23, 1944, and given sulfadiazene therapy. There was still no improvement in either the discharge or the arthritis and on July 1 he had actl.te pain and swelling of the small joints of both hands. The successive joint reactions had caused a gradual febrile response and by July 15 the patient was acutely ill with fever of 102°. The sedimentation rate showed a marked rise from 11 to 103 mm. and leucocyte count to 20,000. Cultures of urine and joint fluid failed to reveal any organisms. The urinary symptoms had continued with such severity that a cystoscope was passed on August 8, 1944. The bladder capacity wlls about an ounce and distention caused bleeding. The mucosa was intensely inflamed and heaped up with an edematous reaction of the whole bladder surface. An exudate covered the walls like a spider web. There was no evidence of any necrotic tissue present. Bladder irrigations were performed on frequent occa:oions using silver nitrate solutions and argyrol. Penicillin was given to the extent of 600,000 units. All of these drugs gave little -relief. Intravenous urograms revealed a dilatation 0f the upper tract and a very much contracted bladder (fig. 1). N ovarsenobenzol was given in small doses 3 times a week, and after the first week of treatment the bladder symptoms began to clear. The arthritis improved, but not until a suppurative focus in the tonsils was discovered and subsequently removed did the patient obtain much symptomatic relief. He was out of bed on October 15 and discharged from the hospital 2 weeks later. We were able to trace this man after a year's absence and discovered he had a recurrence of conjunctivitis and cystitis of mild duration. There was no recurrence of arthritis. Case 2. This 25 year old soldier, Private J. N., reported an acute urethral
262
J. V. BERRY AND N. E. BERRY
discharge to his medical officer in March 1944. A clinical diagnosis of gonorrhoea was made, although there were no typical gonococci reported in the smears. Treatment with sulfathiazole for 5 days brought about cessation of discharge and he was apparently cured. Two weeks later he was admitted to a military hospital with a purpuric vesicular dermatitis and treated first with lead lotion and then with sulfathiazole ointment. The dermatitis was improved slightly but not cured. About 1 week after admission to the hospital he began to complain of dysuria and frequency of urination with terminal hematuria. Rectal examination showed
Fm. 1. Case 1. Contracted bladder with dilated upper urinary·, tract
a tender and boggy prostate but no appreciable enlargement. Hot sitz baths and diathermy were advised with all urinary symptoms becoming aggravated. On June 7, 1944, cystoscopy showed that the bladder was intolerant to more than 2 ounces of fluid. There was intensely acute cystitis with a great deal of adherent exudate. The prostatic urethra, apart from acute congestion, presented no evidence of abscess. The ureteral orifices were not identi'fied because of the marked edema of the trigone. Throughout this period the dermatitis showed numerous exacerbations and remissions, but at not time did it completely disappear. It was confined mainly to the hands and feet, both dorsal and ventral surfaces being affected, the back of the neck and the shoulder regions. During the latter part of July he had pain and swelling of both hands and feet with a low grade fever, and he began to decline markedly in health. There was a loss of 30 pounds in weight and[hc
ACUTE EXUDATIVE CYSTITIS
263
showed a marked degree of anemia. Frequency of urination and strangury had become intolerable with gross hematuria. Intravenous urograms showed marked dilatation of both lower ureters and an appreciable dilatation of both renal pelves. He continued to suffer a good deal; increasing pain in the hands and feet developed, and the left knee and right elbow became involved. This was accompanied by an exacerbation of fever to 101 °. On September 1, 1944, he was started on a course of N ovarsenobenzol 0.3 gm. and this was repeated 4 days later. Definite improvement followed and his temperature fell to normal. Penicillin was now available and a course of 200,000 units was given with further improvement and he became progressively better. By October 1 his joints and his bladder were virtually normal. This was confirmed by cystoscopy and ureteral catheterization was carried out without obstruction. Pyelograms showed now only a slight dilatation on both sides. Case 3. A 24 year old, married, Air Force Sergeant, S. T., with 4 years' military service in Canada, reported a purulent urethral discharge to his medical officer on July 1, 1945. There was no history of exposure and the urethritis was reported as non-specific. After 3 weeks' sulfa therapy the discharge became gradually worse and he was admitted to a military hospital for further investigation. On admission to hospital he began to complain of some frequency of urination which rapidly became worse and on July 30 cystoscopy was reported as showing marked cystitis with edema and swelling of the posterior urethra and bladder neck. Bacteriological examination of the urine showed sterile pyuria. Following the examination he experienced acute pain with frequency every 5 minutes and hematuria so gross that clots retarded the act of urination. The symptoms appeared to improve somewhat in the first course of 900,000 units of penicillin. The relief of symptoms was soon followed by a severe relapse and despite the use of penicillin and sulfa therapy the patient experienced a 3 weeks' period of excruciating pain and frequency. For the next 3 months the symptoms were almost static with intervals of relief from hematuria and strangury, but with frequency of no less than ½hourly intervals. During the first week in November acute bilateral epididymitis developed. On his admission to the London Military Hospital on December 3, 1945, he appeared quite undernourished and pale with considerable loss of weight but not acutely ill. Cystoscopic examination was performed the next day under pentothal anesthesia. A stricture, which barely permitted a 16 F. cystoscope, was detected in the perineal urethra. The bladder capacity was 1½ounces and the bladder mucosa presented patchy areas of acute inflammation with numerous hemorrhagic areas about the floor and neck of the bladder. The ureteral orifices were swollen and would only admit a, 4 F. bougie with difficulty. The orifices were dilated and catheters were passed which revealed clear urine but bilateral hydronephroses (fig. 2, A). December 11, 1945, 0.3 gm. Novarsenobenzol was given for 3 consecutive days with complete relief of hematuria and relief of frequency for 2 hour inter-
264
J. V. BERRY AND N. E. BERRY
vals. After 6 injections the patient took his 2 weeks' Christmas leave and returned with aggravation of symptoms and occasional hematuria. Cystoscopy was repeated, and on this examination the flame-like hemorrhages had disappeared. Over the same areas of the bladder, small blood cysts appeared which on pathological section proved to be hemangiomata. On February 1 (one month later) the hemangiomata had disappeared, leaving numerous small bleeding ulcers with bright hemorrhagic margins. By the end of February 1946, the patient had received a total of 14 injections of N ovarsenobenzol, with relief of his bladder symptoms but with i,ome microscopic hematuria. On March 15, the bladder capacity had reached 3 ounces.
Frn. 2. Case 3. A, Dilated upper urinary tract.
B, After treatment
There were a few small ulcers about the trigone and ureteral orifices appeared q_uite normal; considerable dilatation of the upper tract however remained. Although this man has recovered from the acute bladder lesion, he has written to me recently to state that his doctor is still giving him periodic dilatations of -the bladder. The last intravenous urogram taken on June 12 showed the lleft renal pelvis normal in size and contour but the right side still showed a mild degree of dilatation (fig. 2, B). ETIOLOGY
The cause of the condition is unknown. A filterable virus has been suggested. It has also been thought to be due to focal infection with toxine in the urine
ACUTE EXUDATIVE CYRTTTTR
265
provoking the reaction or that it may be due to a deep-seated coccal infection in the renal parenchyma. It seems to us significant that in all onr cases therewas antecedent urethritis and, with one exception, this was non-specific. Admittedly, we know little about the cause of non-specific urethritis but there is the possibility that it may be specific, the o"ganism not yet being identified. The consistently negative smears and cultures in a condition which is obviously inflammatory can lead only to this conclusion. DIAGNOSIS
The differential diagnosis concerns the exclusion, first, of gonorrhoeal urethritis and prostatitis, and secondly, tuberculosis. The clinical picture and bladder appearances are highly suggestive of renal tuberculosis. The sterile
mil
Frn. 3. Contracted bladder with dilated upper tract with whole process reversed in 17 days after institution of specific treatment.
urine adds to the evidence. A diagnosis of tuberculosis should not be made without proof of the presence of tubercle bacilli. One is apt to linger too long under the impression that these cases may be prostatitis, the prostate being exquisitely tender and often presenting a boggy sensation. This is, however, due to the intense cystitis and ,Yhen properly treated there is not usually any residual prostatic infection. Carcinoma of a diffusely infiltrating type might be a problem to differentiate, but should not be difficult. Familiarity with the syndrome makes the diagnosis obvious. The finding on x-ray of a contracted bladder with dilated ureters and renal pelves is very suggestive of this condition. Characteristically this whole process can be reversed in a short period of time with specific treatment and we believe that such an observation is diagnostic of the disease (fig. 3).
266
J. V. BERRY AND N. E. BERRY
PATHOLOGY
Hess was one of the first to contribute any pathological information on the lesion of acute hemorrhagic cystitis. The early lesion is hemorrhage with mild inflammation of the mucosal stroma. Later vascular channels form in the hemorrhagic areas and finally develop to form hemangiomata. In the terminal stage the mucosa lining the hemangiomata breaks down due to thrombosis, the result of inflammation and scarring, with the formation of punctate ulcers which may appear necrotic but which usually present a hemorrhagic margin. Peters has compared these pathological changes in the bladder typical -0f the clinical entity known as Hun:iier's ulcer. Since no organisms could be demonstrated in the urine, sections of tissue from the bladder were macerated and spread on culture media with negative results. Smears of urethrrl and conjunctival discharges and joint effusions yielded negative findings. The blood picture was typically secondary hypo-chromic anemia. The leucocyte response and sedimentation rate was noted to rise and fall in relation to the acuteness of the joint lesions. Apart from'some ,coincidental findings, the laboratory data were of little interest in the1whole :series. TREATMENT
The treatment is simplified by correct and early diagnosis, though not all the patients tend to respond in the same way. Local treatment of many kinds has been tried by intermittent and' continuous bladder drainage but all were limited by the highly sensitive and intolerant bladders. Mandelic acid and sulfonamides were of little value. Penicillin has not been generally effective but seemed definitely of value in one of our cases. N eoarsphenamine in small
A series of 24 cases of acute exudative cystitis is presented, 3 in detail. A :few cases were complicated by arthritis, .conjunctivitis, iritis and dermatitis. The acute vesical syndrome is characterized by a profuse abacterial pyuria :and gross hematuria. The end result of the inflammatory lesion is a contracted :and ulcerated bladder with terminal ureteritis and marked dilatation of the upper urinary tract. We believe that the condition is caused by an organism, possibly a spirochete :and has some relation to non-specific urethritis. Differential diagnosis concerns the exclusion of gonorrhoea, tuberculosis and malignancy. Familiarity with the symptoms and the urographic findings makes the diagnosis simple. Characteristically the whole picture can be reversed in a short period of time
ACUTE EXUDA'l'IVE CYSTITIS
with specific treatment, the neoarsphenamines being usually employed. harsen, in our experience, is equally efficacious.
Medical Arts Bldg., Ottawa, Canada (J.V.B.) Kingston, Ontario, Canada (:N.E.B.) REFERENCES BRIGGS, W. I.: J. Urol., 34: 230, 1935. COLBY, F. H.: J. Urol., 52: 415, 1944. -CooK, E. N.: Proc. Staff Meet. Mayo Clinic, 19: 377, 1944. HEss, E.: Personal communication. LEVER, W. F. AND CRAWFORD, G. M.: Arch. Dermat. & Syphil., 49: 389, 1944. MILLER, C. D. AND McINTYRE, D. W.: Ann. Int. Med., 23: 673, 1945. MooRE, T.: J. Urol., 49: 203, 1943. PETERS, D. 0.: Brit. Med. J., 1: 160, 1946. SARGENT, J.C.: J. Urol., 54: 556, 1945.
267
Map-