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Cystitis Emphysematosa (1) In An Elderly Diabetic Woman; (2) In A Three-Months-Old Female Infant
CYSTITIS EMPHYSEMATOSA (l) IN AN ELDERLY DIABETIC WOMAN; (2) IN A THREE-MONTHSOLD FEMALE INFANT S. SANES
AND
GEORGE D. DOROSHOW
From Ilic Pathological Labomtory, Buffalo General and Children's Hospi:tals, and the School ol Medicine, Uniilersity
ol Ruffalo
Received for publication June 1, 1934
As an introduction to the disease which this paper discusses, the remarks of Hueper (13) may be appropriately paraphrased: Cystitis cmphysematosa is a term applied to the presence of gas-containing vesicles and cysts in the wall of the urinary bladder, often associated with an inflammatory process. 'Ihe condition is not to be confused with gas formation resulting from putrefactive post-mortem changes, nor is it part of an infection caused by gas gangrene bacilli. In certain etiologic and histologic respects it resembles pneumatosis intestinalis and colpitis emphysematosa. Cystitis emphysematosa has been observed as an incidental post-mortem finding in human beings on 24 occasions (1~8). Cases have also been noted in the cow (11), pig (12), and dog (13). According to reports, the lesion was diagnosed in 2 patients during life (9, 10). The object of this paper is to report the clinical, pathologic and bacteriologic findings in 2 additional examples of cystitis emphysematosa, first discovered at autopsy, and to point out various factors, present in these cases, which may possess general etiologic and pathogenetic significance. REPORT OF CASES
Case 1. Mrs. C F., sixty-two-year-old, white, housewife, was admitted to the Buffalo General Hospital in the service of Dr. Nelson G. Russell, September 26, 1931, in a semi-comatose condition; she died eight hours after entry. For fifteen years the patient had been a known diabetic. In 1924 she was seized with a "stroke." Prior to hospital admission she became drowsy. There was frequency of urination. Physical examination revealed a semi-comatose, senile, white female. Temperature varied from 100° to 101 °F. A fa.cial palsy was presen L Laboratory lindings included: urine:reaction, acid; sugar, four-plus; blood:glucose, 790 mm. per 100 cc.; CO2 combining power, 28 mm. of mercury. 278
CYSTITIS EMPHYSEM/\TOS,\
The autopsy was made one hour after death. The chief anatomic comprised marked generalized arteriosclerosis with calcification especially of vertebral and basilar arteries, with marked narrowing of lurnina; focal white FH:. 2
F1G
Frcs. 4
3 CAST:
FIG.
1
L Gas spaces in mucosa and submucosa; absence of surface epilhcliurn cxccpl in
crypts.
Frc. 2. Gas spaces in snbmucosa and muscularis; surface epithelium preserved F1G. 3. Multinucleated giant cell immediately adjacent to gas space. FrG. 4. Inflammalory reaction in submucosa with edema, neutrophils, cosinophils, and giant cells.
malacia in right side of pons; atrophy of brain with slighl internal lwdrncephalus; marked atrophy of pancreas: cystitis emphysematosa. Description of bladder. "The bladder was distended. lt contained alJ011i.
280
S. SANES AND GEORGE D: DOROSHOW
400 cc. of slightly turbid, yellow urine which issued from the urethra, on vesical pressure, with a sizzling sound. The urine, seemingly charged with gas bubbles, resembled carbonated lemon-water. When the bladder was opened, the mucosa rolled upward into the lumen. To palpation, the vesical wall felt like a rubber sponge. Uniformly, throughout its whole surface the mucosa exhibited myriads of white, dew-like vesicles, crepitant in character and varying from pinhead to split-pea in size. The surface was irregularly flecked red and brown from hemorrhage. The whole appearance with its foamy white, spotted brown color mimicked that of lightly beaten egg whites over which vanilla extract had been sprinkled. On section the mucosa measures 0.2 to 0.3 cm. in thickness; the wall 1.2 cm. When the bladder was placed in water, it floated. Histological examination. In many places the vesical epithelium was deficient. This absence was especially notable over gas vesicles in mucosa; the epithelium was still preserved in crypts and in areas of mucosa directly under which no gas formation was present. Occasionally the epithelium appeared atrophic. The subepithelial tissue and submucosa showed marked congestion, edema and diffuse infiltration of round cells, eosinophile cells, plasma cells and leucocytes. Focal collections of round cells and recent and old hemorrhages were also seen. The inflammatory process extended into the muscle layers. In the submucosa and muscle layers, as in the mucosa, were many oval and circular open spaces. Some of these which possessed an endothelial lining were apparently distended lymphatics. Other spaces showed no specific lining; fibrous tissue formed their walls. Many spaces communicated with each other; some contained red blood cells. Surrounding several spaces in submucosa and muscle layers were giant cells with several nuclei; endothelial giant cells lined distended lymphatics. Many multi-nucleated giant cells were scattered in the inflammatory granulation tissue, in no direct relation to gas spaces. The whole picture corresponrled to a chronic, apparently recurrent cystitis with marked inflammatory edema, with infiltration of round cells, eosinophile and plasma cells and leucocytes, and with extensive recent hemorrhage and signs of old hemorrhages. In addition, diffuse, advanced emphysema honeycombed the tissue and distended lymph spaces in all layers. Bacteriologic findings. Smears from surface of bladder and from gas vesicles showed small, plump, Gram-negative bacilli. No other organisms were seen. Culture of urine disclosed Gram-negative bacillus closely allied to B. coli communis which did not form acid or gas in sucrose, but which did ferment lactose and dextrose. Cultures from bladder taken after fixation in formaldehyde were sterile. Methylene blue and Gram-Weigert stains on thin, paraffine sections revealed Gram-negative bacilli in tissue.
CYSTITIS EMPHYSEMA TOSA
281
Case 2. 1) M., three-month-old, white, female infant was admitted to the Buffalo Children's Hospital in the service of Dr. .DeWitt H. She1man on February 21, 1934, because of fever of three weeks' duration. She died on March 9, 1934. The patient, an only child, was well until February 6, 1934, when she FIG. 5
FIC. (i
Fie. S. Internal view of bladder showing gas bubbles slightly obscured by high lights. FIG. 6. Gas spaces in mucosa; absence of surface epithelium.
began to refuse feedings. On February 13, 1934, the mother first detected a fever that persisted with daily fluctuations. The child cried whenever she urinated. On admiEsion, physical examination revealed only a sick, feverish child. Radiographic examination of the lungs was negative. The urine showed many pus cells. The clinical impression was pyuria.
282
S. SANES AND GEORGE D. DOROSHO"\Y
In the hospital the temperature ranged from 99° to 103°F. On February 24, 1934, a mass was palpated in the left upper quadrant. On March 1, 1934, cystoscopy disclosed a bladder which possessed a large capacity and which contained cloudy urine. The left ureteral opening was large and gaping; number four catheter passed easily. Following injection of -1- cc. SO per cent skiodan, x-ray films showed a small left pelvis with suggestion of rotation. The right ureter was not catheterized. The child received three transfusions. Glucose water (2.5 per cent) was given by mouth every two hours. Hypodermoclysis of S per cent glucose was administered twice
CYSTITIS EMPHYSEMATOSA
283
ever, exhibited edema and scattered leucocytes and round cells. A tributary lymphnode which was examined contained no gas spaces. Bacteriologic findings . Smears from urine, bladder, mucosa, and pleura revealed only short, Gram-negative bacilli. Cultures from urine, bladder wall and spleen were positive for B. coli communis. COMMENT
The gross and histologic descriptions of our specimens can serve as representative examples of the two contrastive forms by which cystitis emphysematosa usually manifests itself. In the first case, the entire mucosal surface and the wall throughout its whole depth were involved by gas vesicles. The inflammatory reactionwasmarked; multi-nucleated and endothelial giant cells were present. In the second instance, the gas vesicles were solitary and scattered in spots, localized especially to the posterior wall; they had not advanced beyond the tunica propria. Cellular infiltration was minimal; giant cells were lacking. Diffuse congestion, hemorrhages, and epithelial desquamation characterized both cases. In regard to the etiology and pathogenesis of cystitis emphysematosa, concerning which there has been much controversy, our cases displayed several significant features: viz., bacteriologic data, reaction of urine, residual urine, distension of bladder, ureteral anomaly, instrumentation, vesical congestion, hemorrhage and inflammation, high blood glucose, the age and sex of the patients. While the scarcity of gas vesicles in case 2 might support Schoneberg's (5) belief that the emphysematous process is entirely agonal in origin, case 1 in which giant cells apparently of the foreign body type were observed in relation to emphysematous spaces, prevents the acceptance of such a conception as an universal explanation. In each of our cases a bacillus of the colon group was isolated from urine and in bladder wall. Of interest is the fact that the cystitis emphysematosa in the second patient developed as a terminal incident in a known B . coli cystopyelonephritis and consequent septicemia. Impressed by the frequent presence of B. coli in cystitis emphysematosa (1, 2, 3, 5, 6), and cognizant of the accepted role of the same organism in pneumatosa intestinalis, Nowicki (6) even went so far as to formulate the theory that cystitis emphysematosa is the result of an infection of the urinary bladder with colon bacilli which have gained entrance from the blood stream or through a damaged epithelium. From a theoretical
284
S. SANES AND GEORGE D. DOROSHOW
standpoint, it seems to us justifiable to consider the possibility of other gas-forming bacilli as etiologic agents. Schoneberg (5) recovered streptococcus in one of his cases; Mills (7) obtained a blood culture, positive for pneumococcus. The appearance and gross of colon bacilli in children with urinary anomalies and in invalids who do not void completely are known. Distension, congestion, hemorrhage, and desquamative inflammation have been blamed for alterations in the bladder mucosa which allow ready invasion of bacteria. To what degree hemorrhage and desquamation may be secondary to gas formation, it is difficult to judge. In our second case cystoscopy was performed one week before the death of the patient. At that time gas vesicles were not seen. Catheterization was resorted to several times. Mills (7) stressed the point that in a majority of his cases bladder instrumentation (by catheter, cystoscope and fulgurator) was made. In a few bladders of this group the emphysematous lesion was localized in the posterior wall, once sharply above the trigone, where an instrument could be expected to impinge. The mechanism of gas formation in cystitis emphysematosa has never been adequately settled. Regularly, bladders are seen showing desquamation, ulceration, hemorrhages, denuded polyps and bacterial infection, in which gas has not been produced. With this fact in mind, it seems reasonable to expect in the isolated cases of cystitis emphysematosa certain factors predisposing to gas formation. We know that with an increased sugar content in the blood, sugar diffuses into lymph and tissue. Further, various bacteria, such as B. coli, thrive and liberate gas in specific carbohydrate media. Pneumatosis intestinalis is more common in animals, which live by natural inclination or for experimental purposes on a high carbohydrate diet (14). With no attempt to draw general conclusions, we wish to indicate that along with Schoneberg's and Hueper's cases our first patient was diabetic with a high blood and urine glucose. In our second patient 2 .5 per cent glucose water was given every two hours by mouth, and 5 per cent glucose solution was administered subcutaneously during the last days of life. While the blood glucose was not estimated, a routine sample of urine six days before the death of the patient showed 1-plus copper reduction. Fully three-fourths of Mills' patients received parenteral injections of glucose. It is interesting to note that in the last four years at the Buffalo General Hospital infections (four cases) with gas formation due to Welch bacillus and streptococcus have occurred solely in diabetics (15). Hitschman and Lindenthal (16) at one time thought that the colon bacillus produced gas only
CYSTITIS EMPHYSEMATOSA
285
in diabetic patients. Recently Warren (17) referred to B. coli infection of subcutaneous tissue in diabetics with gas formation; Reiss (18) obthe anterior chamber of the eye of a diabetic who served gas bubbles was suffering from B. coli enophthalmia. The work of Hubbard and Vaughan (19) does not support the explanation, propounded for cases without demonstrable organisms in bladder wall (4, 13) that B. coli in the urine may produce diffusible enzymes, which upon absorption into the bladder wall, ferment carbohydrate. Among the 26 reported cases of cystitis emphysematosa, 19 were female; 7, male. The ages of the patients ranged from twelve to seventyseven years. Both of our patients were female. Our second patient is the youngest, in whom the emphysematous lesion has been seen. SUMMARY
Two examples of cystitis emphysematosa which were accidentally discovered at autopsy are described because of their rarity and their etiologic and pathogenetic implications. The gross and histologic findings exemplified advanced and early lesions, respectively. In each case a bacillus of the colon group was demonstrated in the urine and in bladder walL Both patients were female.. The first was an elderly, diabetic invalid with high blood and urine glucose. The second patient, aged three months, is the first infant and the youngest individual in whom cystitis emphysematosa has been observed. Clinically, she suffered from B. coli cystopyelonephritis and septicemia. In therapy, glucose was administered orally and subcutaneously; cystoscopy and catheterization were performed. A complete bibliography is appended. We are indebted to Dr. K. Terplan for helpful suggestions and criticism. REFERENCES Human cases (1) (2) (3) (4) (5) (6) (7)
ErsENLOHR, W.: Beitr. z. Path. Anat. u.z. Allg. Path., 1888, iii, 101. CAMARGO, A.: These de Geneve, 1891. KEDR0WSKY, W. J.: Centralbl. f. Alig. Path. u. Path. Anat., 1898, ix, 1817. RuPPANNER, E.: Frank£. Ztschr. f. Path., 1903, ii, 343. ScH0NEBERG, S.: Frankf. Ztschr. f. Path., 1913, xii, 289. NowrcKr, W.: Virchow's Arch. f. Path. Anat., 1914, cv, 126, 1924, cliii, L MILLS, R. G.: Jour. Amer. Med. Assoc., 1930, xciv, 321; Jour. Urol., 1930, xxiii, 289; Amer. Jour. Obstet. and Gynec., 1930, xx, 688; Jour. Urol., 1930, xxiv, 217; Surg., Gynecol. and Obstet., 1930, li, 545.
286
S. SANES AND GEORGE D. DOROSHOW
(8) WILDBOLZ, HANS: Lehrbuch der Urologie. Berlin, Julius Springer, 311, 1924. Cited by Mills. (9) LAUTENSCHLAGER, E. L.: Inaug. Diss. Heidelberg. C. Belser, Stuttgart, 1911. Cited by Mills. {10) RAVICH, A., AND KATZEN, P.: Jour. Amer. Med. Assoc., 1932, xcviii, 1256. Animal cases (11) KITT: Lehrbuch der Pathologischen Anatomie der Haustiere. 3rd ed., vol. 1, 663. Cited by Hueper. (12) OLT: Beitr. z. Path. Anat. u.z. Alig. Path., 1921, lxi~, 549. (13) HuEPER, W. C.: Amer. Jour. Path., 1926, ii, 159. Other references {14) RossI: Estratto de! giornale II nuovo ercolani, anno XV, 1910, num. 15 and 16. Cited by Hueper. (15) BOWEN, B. D . : Personal communication. (16) HITSCHMAN AND LINDENTHAL: Sitzungesber. d . math. naiurfor. d'Akad. d Wissensch. Wien., 1901. Cited by Nowicki. (17) WARREN, SmELDS: Pathology of diabetes. Read before the Buffalo Academy of Medicine, November, 1932. (18) REISS, W.: Polska gas. lek., 1930, ix, 570; Klin. Monatsbl. f. Augenh., 1929, lxxxiii, 784. (19) HUBBARD, R. S., AND VAUGHAN, S. L.: Proc. Soc. Exp. Biol. and Med., 1932, xxx, 407.
AND
GEORGE D. DOROSHOW
From Ilic Pathological Labomtory, Buffalo General and Children's Hospi:tals, and the School ol Medicine, Uniilersity
ol Ruffalo
Received for publication June 1, 1934
As an introduction to the disease which this paper discusses, the remarks of Hueper (13) may be appropriately paraphrased: Cystitis cmphysematosa is a term applied to the presence of gas-containing vesicles and cysts in the wall of the urinary bladder, often associated with an inflammatory process. 'Ihe condition is not to be confused with gas formation resulting from putrefactive post-mortem changes, nor is it part of an infection caused by gas gangrene bacilli. In certain etiologic and histologic respects it resembles pneumatosis intestinalis and colpitis emphysematosa. Cystitis emphysematosa has been observed as an incidental post-mortem finding in human beings on 24 occasions (1~8). Cases have also been noted in the cow (11), pig (12), and dog (13). According to reports, the lesion was diagnosed in 2 patients during life (9, 10). The object of this paper is to report the clinical, pathologic and bacteriologic findings in 2 additional examples of cystitis emphysematosa, first discovered at autopsy, and to point out various factors, present in these cases, which may possess general etiologic and pathogenetic significance. REPORT OF CASES
Case 1. Mrs. C F., sixty-two-year-old, white, housewife, was admitted to the Buffalo General Hospital in the service of Dr. Nelson G. Russell, September 26, 1931, in a semi-comatose condition; she died eight hours after entry. For fifteen years the patient had been a known diabetic. In 1924 she was seized with a "stroke." Prior to hospital admission she became drowsy. There was frequency of urination. Physical examination revealed a semi-comatose, senile, white female. Temperature varied from 100° to 101 °F. A fa.cial palsy was presen L Laboratory lindings included: urine:reaction, acid; sugar, four-plus; blood:glucose, 790 mm. per 100 cc.; CO2 combining power, 28 mm. of mercury. 278
CYSTITIS EMPHYSEM/\TOS,\
The autopsy was made one hour after death. The chief anatomic comprised marked generalized arteriosclerosis with calcification especially of vertebral and basilar arteries, with marked narrowing of lurnina; focal white FH:. 2
F1G
Frcs. 4
3 CAST:
FIG.
1
L Gas spaces in mucosa and submucosa; absence of surface epilhcliurn cxccpl in
crypts.
Frc. 2. Gas spaces in snbmucosa and muscularis; surface epithelium preserved F1G. 3. Multinucleated giant cell immediately adjacent to gas space. FrG. 4. Inflammalory reaction in submucosa with edema, neutrophils, cosinophils, and giant cells.
malacia in right side of pons; atrophy of brain with slighl internal lwdrncephalus; marked atrophy of pancreas: cystitis emphysematosa. Description of bladder. "The bladder was distended. lt contained alJ011i.
280
S. SANES AND GEORGE D: DOROSHOW
400 cc. of slightly turbid, yellow urine which issued from the urethra, on vesical pressure, with a sizzling sound. The urine, seemingly charged with gas bubbles, resembled carbonated lemon-water. When the bladder was opened, the mucosa rolled upward into the lumen. To palpation, the vesical wall felt like a rubber sponge. Uniformly, throughout its whole surface the mucosa exhibited myriads of white, dew-like vesicles, crepitant in character and varying from pinhead to split-pea in size. The surface was irregularly flecked red and brown from hemorrhage. The whole appearance with its foamy white, spotted brown color mimicked that of lightly beaten egg whites over which vanilla extract had been sprinkled. On section the mucosa measures 0.2 to 0.3 cm. in thickness; the wall 1.2 cm. When the bladder was placed in water, it floated. Histological examination. In many places the vesical epithelium was deficient. This absence was especially notable over gas vesicles in mucosa; the epithelium was still preserved in crypts and in areas of mucosa directly under which no gas formation was present. Occasionally the epithelium appeared atrophic. The subepithelial tissue and submucosa showed marked congestion, edema and diffuse infiltration of round cells, eosinophile cells, plasma cells and leucocytes. Focal collections of round cells and recent and old hemorrhages were also seen. The inflammatory process extended into the muscle layers. In the submucosa and muscle layers, as in the mucosa, were many oval and circular open spaces. Some of these which possessed an endothelial lining were apparently distended lymphatics. Other spaces showed no specific lining; fibrous tissue formed their walls. Many spaces communicated with each other; some contained red blood cells. Surrounding several spaces in submucosa and muscle layers were giant cells with several nuclei; endothelial giant cells lined distended lymphatics. Many multi-nucleated giant cells were scattered in the inflammatory granulation tissue, in no direct relation to gas spaces. The whole picture corresponrled to a chronic, apparently recurrent cystitis with marked inflammatory edema, with infiltration of round cells, eosinophile and plasma cells and leucocytes, and with extensive recent hemorrhage and signs of old hemorrhages. In addition, diffuse, advanced emphysema honeycombed the tissue and distended lymph spaces in all layers. Bacteriologic findings. Smears from surface of bladder and from gas vesicles showed small, plump, Gram-negative bacilli. No other organisms were seen. Culture of urine disclosed Gram-negative bacillus closely allied to B. coli communis which did not form acid or gas in sucrose, but which did ferment lactose and dextrose. Cultures from bladder taken after fixation in formaldehyde were sterile. Methylene blue and Gram-Weigert stains on thin, paraffine sections revealed Gram-negative bacilli in tissue.
CYSTITIS EMPHYSEMA TOSA
281
Case 2. 1) M., three-month-old, white, female infant was admitted to the Buffalo Children's Hospital in the service of Dr. .DeWitt H. She1man on February 21, 1934, because of fever of three weeks' duration. She died on March 9, 1934. The patient, an only child, was well until February 6, 1934, when she FIG. 5
FIC. (i
Fie. S. Internal view of bladder showing gas bubbles slightly obscured by high lights. FIG. 6. Gas spaces in mucosa; absence of surface epithelium.
began to refuse feedings. On February 13, 1934, the mother first detected a fever that persisted with daily fluctuations. The child cried whenever she urinated. On admiEsion, physical examination revealed only a sick, feverish child. Radiographic examination of the lungs was negative. The urine showed many pus cells. The clinical impression was pyuria.
282
S. SANES AND GEORGE D. DOROSHO"\Y
In the hospital the temperature ranged from 99° to 103°F. On February 24, 1934, a mass was palpated in the left upper quadrant. On March 1, 1934, cystoscopy disclosed a bladder which possessed a large capacity and which contained cloudy urine. The left ureteral opening was large and gaping; number four catheter passed easily. Following injection of -1- cc. SO per cent skiodan, x-ray films showed a small left pelvis with suggestion of rotation. The right ureter was not catheterized. The child received three transfusions. Glucose water (2.5 per cent) was given by mouth every two hours. Hypodermoclysis of S per cent glucose was administered twice
CYSTITIS EMPHYSEMATOSA
283
ever, exhibited edema and scattered leucocytes and round cells. A tributary lymphnode which was examined contained no gas spaces. Bacteriologic findings . Smears from urine, bladder, mucosa, and pleura revealed only short, Gram-negative bacilli. Cultures from urine, bladder wall and spleen were positive for B. coli communis. COMMENT
The gross and histologic descriptions of our specimens can serve as representative examples of the two contrastive forms by which cystitis emphysematosa usually manifests itself. In the first case, the entire mucosal surface and the wall throughout its whole depth were involved by gas vesicles. The inflammatory reactionwasmarked; multi-nucleated and endothelial giant cells were present. In the second instance, the gas vesicles were solitary and scattered in spots, localized especially to the posterior wall; they had not advanced beyond the tunica propria. Cellular infiltration was minimal; giant cells were lacking. Diffuse congestion, hemorrhages, and epithelial desquamation characterized both cases. In regard to the etiology and pathogenesis of cystitis emphysematosa, concerning which there has been much controversy, our cases displayed several significant features: viz., bacteriologic data, reaction of urine, residual urine, distension of bladder, ureteral anomaly, instrumentation, vesical congestion, hemorrhage and inflammation, high blood glucose, the age and sex of the patients. While the scarcity of gas vesicles in case 2 might support Schoneberg's (5) belief that the emphysematous process is entirely agonal in origin, case 1 in which giant cells apparently of the foreign body type were observed in relation to emphysematous spaces, prevents the acceptance of such a conception as an universal explanation. In each of our cases a bacillus of the colon group was isolated from urine and in bladder wall. Of interest is the fact that the cystitis emphysematosa in the second patient developed as a terminal incident in a known B . coli cystopyelonephritis and consequent septicemia. Impressed by the frequent presence of B. coli in cystitis emphysematosa (1, 2, 3, 5, 6), and cognizant of the accepted role of the same organism in pneumatosa intestinalis, Nowicki (6) even went so far as to formulate the theory that cystitis emphysematosa is the result of an infection of the urinary bladder with colon bacilli which have gained entrance from the blood stream or through a damaged epithelium. From a theoretical
284
S. SANES AND GEORGE D. DOROSHOW
standpoint, it seems to us justifiable to consider the possibility of other gas-forming bacilli as etiologic agents. Schoneberg (5) recovered streptococcus in one of his cases; Mills (7) obtained a blood culture, positive for pneumococcus. The appearance and gross of colon bacilli in children with urinary anomalies and in invalids who do not void completely are known. Distension, congestion, hemorrhage, and desquamative inflammation have been blamed for alterations in the bladder mucosa which allow ready invasion of bacteria. To what degree hemorrhage and desquamation may be secondary to gas formation, it is difficult to judge. In our second case cystoscopy was performed one week before the death of the patient. At that time gas vesicles were not seen. Catheterization was resorted to several times. Mills (7) stressed the point that in a majority of his cases bladder instrumentation (by catheter, cystoscope and fulgurator) was made. In a few bladders of this group the emphysematous lesion was localized in the posterior wall, once sharply above the trigone, where an instrument could be expected to impinge. The mechanism of gas formation in cystitis emphysematosa has never been adequately settled. Regularly, bladders are seen showing desquamation, ulceration, hemorrhages, denuded polyps and bacterial infection, in which gas has not been produced. With this fact in mind, it seems reasonable to expect in the isolated cases of cystitis emphysematosa certain factors predisposing to gas formation. We know that with an increased sugar content in the blood, sugar diffuses into lymph and tissue. Further, various bacteria, such as B. coli, thrive and liberate gas in specific carbohydrate media. Pneumatosis intestinalis is more common in animals, which live by natural inclination or for experimental purposes on a high carbohydrate diet (14). With no attempt to draw general conclusions, we wish to indicate that along with Schoneberg's and Hueper's cases our first patient was diabetic with a high blood and urine glucose. In our second patient 2 .5 per cent glucose water was given every two hours by mouth, and 5 per cent glucose solution was administered subcutaneously during the last days of life. While the blood glucose was not estimated, a routine sample of urine six days before the death of the patient showed 1-plus copper reduction. Fully three-fourths of Mills' patients received parenteral injections of glucose. It is interesting to note that in the last four years at the Buffalo General Hospital infections (four cases) with gas formation due to Welch bacillus and streptococcus have occurred solely in diabetics (15). Hitschman and Lindenthal (16) at one time thought that the colon bacillus produced gas only
CYSTITIS EMPHYSEMATOSA
285
in diabetic patients. Recently Warren (17) referred to B. coli infection of subcutaneous tissue in diabetics with gas formation; Reiss (18) obthe anterior chamber of the eye of a diabetic who served gas bubbles was suffering from B. coli enophthalmia. The work of Hubbard and Vaughan (19) does not support the explanation, propounded for cases without demonstrable organisms in bladder wall (4, 13) that B. coli in the urine may produce diffusible enzymes, which upon absorption into the bladder wall, ferment carbohydrate. Among the 26 reported cases of cystitis emphysematosa, 19 were female; 7, male. The ages of the patients ranged from twelve to seventyseven years. Both of our patients were female. Our second patient is the youngest, in whom the emphysematous lesion has been seen. SUMMARY
Two examples of cystitis emphysematosa which were accidentally discovered at autopsy are described because of their rarity and their etiologic and pathogenetic implications. The gross and histologic findings exemplified advanced and early lesions, respectively. In each case a bacillus of the colon group was demonstrated in the urine and in bladder walL Both patients were female.. The first was an elderly, diabetic invalid with high blood and urine glucose. The second patient, aged three months, is the first infant and the youngest individual in whom cystitis emphysematosa has been observed. Clinically, she suffered from B. coli cystopyelonephritis and septicemia. In therapy, glucose was administered orally and subcutaneously; cystoscopy and catheterization were performed. A complete bibliography is appended. We are indebted to Dr. K. Terplan for helpful suggestions and criticism. REFERENCES Human cases (1) (2) (3) (4) (5) (6) (7)
ErsENLOHR, W.: Beitr. z. Path. Anat. u.z. Allg. Path., 1888, iii, 101. CAMARGO, A.: These de Geneve, 1891. KEDR0WSKY, W. J.: Centralbl. f. Alig. Path. u. Path. Anat., 1898, ix, 1817. RuPPANNER, E.: Frank£. Ztschr. f. Path., 1903, ii, 343. ScH0NEBERG, S.: Frankf. Ztschr. f. Path., 1913, xii, 289. NowrcKr, W.: Virchow's Arch. f. Path. Anat., 1914, cv, 126, 1924, cliii, L MILLS, R. G.: Jour. Amer. Med. Assoc., 1930, xciv, 321; Jour. Urol., 1930, xxiii, 289; Amer. Jour. Obstet. and Gynec., 1930, xx, 688; Jour. Urol., 1930, xxiv, 217; Surg., Gynecol. and Obstet., 1930, li, 545.
286
S. SANES AND GEORGE D. DOROSHOW
(8) WILDBOLZ, HANS: Lehrbuch der Urologie. Berlin, Julius Springer, 311, 1924. Cited by Mills. (9) LAUTENSCHLAGER, E. L.: Inaug. Diss. Heidelberg. C. Belser, Stuttgart, 1911. Cited by Mills. {10) RAVICH, A., AND KATZEN, P.: Jour. Amer. Med. Assoc., 1932, xcviii, 1256. Animal cases (11) KITT: Lehrbuch der Pathologischen Anatomie der Haustiere. 3rd ed., vol. 1, 663. Cited by Hueper. (12) OLT: Beitr. z. Path. Anat. u.z. Alig. Path., 1921, lxi~, 549. (13) HuEPER, W. C.: Amer. Jour. Path., 1926, ii, 159. Other references {14) RossI: Estratto de! giornale II nuovo ercolani, anno XV, 1910, num. 15 and 16. Cited by Hueper. (15) BOWEN, B. D . : Personal communication. (16) HITSCHMAN AND LINDENTHAL: Sitzungesber. d . math. naiurfor. d'Akad. d Wissensch. Wien., 1901. Cited by Nowicki. (17) WARREN, SmELDS: Pathology of diabetes. Read before the Buffalo Academy of Medicine, November, 1932. (18) REISS, W.: Polska gas. lek., 1930, ix, 570; Klin. Monatsbl. f. Augenh., 1929, lxxxiii, 784. (19) HUBBARD, R. S., AND VAUGHAN, S. L.: Proc. Soc. Exp. Biol. and Med., 1932, xxx, 407.