British Jourrml of Urology (1977), 49, 647-650
0
Abacterial Cystitis P. T. DOYLE, G. F.
ABERCROMBIE, J. D.
JENKINS,
c. J.
SMART
and
J. VINNICOMBE
From rlie Departments of Urology, Portsniouth and Soirtharnpton
Over 30 years ago Moore (1940) described a condition which he called Abacterial Cystitis and there have been several other reports of this condition since (Coutts and Vargas-Zalazar, 1946; Czekalowski and Horne, 1951; Moore, Parker and Charlton Edwards, 1971). The patients had an acute cystitis, their urine contained pus and red blood cells and their intravenous urograms showed appearances similar to those seen in genito-urinary tuberculosis. No bacteria, however, were jsolated from the urine. Over a 10-year period in the Portsmouth and Southampton Districts approximately 80 patients with acute cystitis and an initially sterile urine have presented. Most of these have proved to be genito-urinary tuberculosis, but among them have been the 5 cases we wish to present.
Patients and Results All 5 were male patients whose ages ranged from 18 to 31. There were no common features in their employment. 2 were married and 3 single. They were referred because of the sudden onset of severe urgency and frequency of micturition, with terminal haematuria. 2 patients had a history or urethral discharge which had occurred on and off for a period of some years. 1 of them attended the Portsmouth Special Clinic but no organism was cultured from the discharge. When first seen, all of these patients were micturating every 15 to 30 minutes, day and night. They had noticed terminal haematuria, which was heavy in the youngest patient and had noticed that their urine was cloudy but not offensive. The youngest patient had also noticed bilateral loin pain during micturition. There was n o history of any serious disease in any patient. 4 of them had received antibacterial treatment, but sulphonamides, ampicillin, cephalosporins, nitrofurantoin and nalidixic acid had produced no improvement and the pyuria persisted. Most of the patients looked ill; 1 was admitted directly from Out-patients, a second shortly afterwards when his symptoms deteriorated, and a third as an emergency with increasing haematuria. All were apyrexial. 2 had suprapubic tenderness, and 2 had a tender prostate gland. 1 of the latter had a urethral discharge. The youngest patient was hypertensive, with a blood pressure of lSOjll.5 mm Hg. Repeated mid-stream specimens of urine showed pus and red blood cells, but there was no growth on culture, and repeated cultures for acid-fast bacilli were also negative. Haemoglobin estimations were all within normal limits and whte cell counts varied from 6,000 to 13,000 per mm3, with a normal differential count. In the most severe case the sedimentation rate was 13 rnm per hour. The serum creatinine and urea estimations were normal and there were no other abnormal biochemical findings. The intravenous urogram showed immediate renal function, with normal upper urinary tracts in 2 cases and bilateral clubbed calyces and dilated ureters in 3 cases (Fig. 1). The bladder outline in all the patients was small and irregular (Fig. 2). At cystoscopy the bladder capacity was much reduced and the mucosa intensely congested. The appearances were compatible with a diagnosis Read at the 33rd Annual Merting of the British Association of Urological Surgeons in Aberdeen, June 1977. 647
648
BRITISH JOURNAL OF UROLOGY
of vesical tuberculosis. Bimanual examination was normal with the prostate being reported normal in all cases. Biopsy of the bladder wall showed infiltration by acute and chronic inflammatory cells, including polymorphonuclear leucocytes, histiocytes and occasional lymphocytes, eosinophils and macrophages. In 1 case these changes were present in both bladder and prostatic biopsies. The 2 early cases seen in Portsmouth were not treated at first, as tuberculosis seemed the likely diagnosis, and only after a long series of urine tests proved negative was any other diagnosis suspected. The symptoms in 1 of these patients settled spontaneously, but in the other patient the symptoms persisted unchanged for 4 months. “Abacterial cystitis” was then suspected and treatment with tetracycline was instituted. His symptoms immediately improved. Other patients in the series were treated with tetracycline at a much earlier stage. A standard dosage of 250 mg 4 times daily proved quite sufficient. The blood and pus gradually disappeared from the urine and, in 2 patients, a follow-up intravenous urogram has shown much improved appearances. 3 patients have had a follow-up cystoscopy, one 3 months after treatment when normal appearances were reported, a second after 8 months because of a failing stream. There was
Fig. 1. Intravenous urogram showing typical appearances of small contracted bladder, dilated ureters and clubbed calices. Fig. 2. Intravenous urogram showing irregular contracted bladder with normal upper urinary tracts.
ABACTERIAL CYSTlTIS
649
a short bulbar stricture but the bladder was normal and the stricture settled after out-patient dilatation. A third case had a cystoscopy because of a recurrence of urethral discharge but the bladder appeared quite normal, as did the prostate. The subsequent progress for each patient has been relatively uncomplicated. 1 had perineal aching and pain after intercourse, with occasional urgency of micturition. He has attended the Eye Department with idiopathic retinal haemorrhages, and a diagnosis of Reiter’s disease was considered; however, his symptoms settled and no positive diagnosis was established. The most recent case, who was treated less than a year ago, is symptom free at present. His raised blood pressure on admission had settled at the time of his follow-up cystoscopy 3 months later. Discussion
This condition seems to be a disease of young male patients. Donovan (1946) in his cases described an associated sterile urethral discharge. Goldstein (1947) reported severe cystitis associated with Reiter’s Syndrome. Cultures of the urine in previous reports have never reliably established a cause although Coutts and Vargas-Zalazar (1946) found a spirilla in 5 cases and Czekalowski and Horne (1951) a spirochaete. The bladder seems to be principally affected. The 3 cases reported by Moore et al. (1971) all had normal upper urinary tracts, I patient was hypertensive. Hanky and Stept (1950) mentioned the value of tetracycline in this condition, and Moore et al. (1971) found organic arsenicals useful. The cause of the condition has yet to be established. Although it has been called “Abacterial cystitis” the evidence would suggest that it is an infective condition, in that there is pus and blood in the urine, the bladder mucosa is inflamed, and the symptoms respond to tetracycline. The response to tetracycline makes a viral aetiology unlikely, but the pathogen might be a mycoplasma or chlamydia which is sensitive to tetracycline but not to other commonly used antibacterials. Mycoplasma are known to cause cystitis (Berg, Weinberger and Dienes, 1957). These organisms were not sought either in urine or from urethral discharge in any of our patients. If the pathogen was a bacteria, however, it is possible that it was not detected by the standard culture methods used. Our patients’ mid-stream urines were cultured on MacConkey agar at the time they presented and it has been recognised since then that this medium does not reliably support the growth of Staphylococcus albus, one type of which, the micrococcus, is now known to be a cause of cystitis (Maskell, 1974). Furthermore, there are organisms known to be fastidious in various ways ; they may be slow growing and require a longer incubation time than is usually used, or they may be micro-aerophilic or even anaerobic. Since this problem was discussed with a bacteriologist, our laboratory has recorded 3 cases in which a mid-stream urine sent in by a general practitioner from a young male with acute urinary symptoms showed pyuria and haematuria, but again no organisms on culture by routine techniques. Cultures were repeated using other media and longer incubation, a micrococcus was isolated from one, a strain of Acinetobacter lwoflii from a second, and a coliform from a third. With hindsight, therefore, it is impossible to say that there were no bacteria in these patients’ urines. The diagnosis of “Abacterial cystitis” should not therefore be made until careful bacteriological investigations have been undertaken. In this way, the causative organism or organisms might be established. This condition has a close similarity to genito-urinary tuberculosis and should be remembered in any young male patient with a sterile pyuria in whom acid-fast bacilli cannot be cultured. Summary 5 young male patients with all the symptoms and signs of genito-urinary tuberculosis but in whom no organism could be cultured from the urine are described. 4 of them rapidly responded to a course of tetracycline. 4917-~
650
BRITISH JOURNAL OF UROLOGY
Various organisms are suggested as a cause of this condition, and careful bacteriological investigation in the future might discover the cause. I should like to thank the Surgeons of the Portsmouth and Southampton Districts for allowing me to publish their cases, and Dr R. Maskell of the Bacteriological Department, Saint Mary’s Hospital, Portsmouth, for her helpful advice. I should also like to thank Mr D. MacLean, Medical Photographer, Portsmouth District Hospitals, for his help in the preparation of the illustrations.
References BERG,R. L., WEINBERGER, H. and DIENES,L. (1957). Acute hemorrhagic cystitis, an infection associated with pleuropneumonia-like organisms and related to urethritis and prostatitis. American Journal of Medicine, 22, 848-864. COUTTS,W. E. and VARGAS-ZALAZAR, R. (1946). Abacterial pyuria with special reference to infection by spirochaetes. British Medical Journal, 2, 982-983. CZEKALOWSKI, J. W. and HORNE, G. 0. (1951). Abacterial cystitis: report of three cases and isolation of a spirochaete from one. British Medical Journal, 2, 879-881. DONOVAN, H. (1945). Abacterial pyuria. British Medical Journal, 2, 12-13. A. E. (1947). Reiter’s disease followed by true infective abacterial pyuria. British Journal of Uro/ogy, 19, GOLDSTEIN, 32-34. HANKEY, S . M. and STEPT,R. (1950). Abacterial pyuria, response to aureomycin. Journal of Urology, 63, 912-914. MASKELL, R. (1974). Importance of coagulase-negative staphylococci as pathogens in the urinary tract. Lancet, 1, 1155-1158. MOORE, T. (1940). Sterile pyuria. Proceedings of the Royal Society of Medicine, 33, 593-599. T., PARKER, C. and EDWARDS, E. C. (1971). Sterile non-tuberculous pyuria. British Journal of Urology, 43, MOORE, 47-51.
The Authors P. T. Doyle, FRCS, Senior Registrar, Department of Urology, St. Mary’s General Hospital, Portsmouth. G. F. Abercrombie, FRCS, Consultant Urological Surgeon, Portsmouth and S.E. Hants. Health District. J. D. Jenkins, MChir, FRCS, Consultant Urological Surgeon, Southampton University Hospitals. C. J. Smart, FRCS, Consultant Urologist, Southampton and S.W. Hants. Health District. J. Vinnicombe, MChir, FRCS, Consultant Urological Surgeon, Portsmouth Hospitals Group.
0
Abacterial Cystitis P. T. DOYLE, G. F.
ABERCROMBIE, J. D.
JENKINS,
c. J.
SMART
and
J. VINNICOMBE
From rlie Departments of Urology, Portsniouth and Soirtharnpton
Over 30 years ago Moore (1940) described a condition which he called Abacterial Cystitis and there have been several other reports of this condition since (Coutts and Vargas-Zalazar, 1946; Czekalowski and Horne, 1951; Moore, Parker and Charlton Edwards, 1971). The patients had an acute cystitis, their urine contained pus and red blood cells and their intravenous urograms showed appearances similar to those seen in genito-urinary tuberculosis. No bacteria, however, were jsolated from the urine. Over a 10-year period in the Portsmouth and Southampton Districts approximately 80 patients with acute cystitis and an initially sterile urine have presented. Most of these have proved to be genito-urinary tuberculosis, but among them have been the 5 cases we wish to present.
Patients and Results All 5 were male patients whose ages ranged from 18 to 31. There were no common features in their employment. 2 were married and 3 single. They were referred because of the sudden onset of severe urgency and frequency of micturition, with terminal haematuria. 2 patients had a history or urethral discharge which had occurred on and off for a period of some years. 1 of them attended the Portsmouth Special Clinic but no organism was cultured from the discharge. When first seen, all of these patients were micturating every 15 to 30 minutes, day and night. They had noticed terminal haematuria, which was heavy in the youngest patient and had noticed that their urine was cloudy but not offensive. The youngest patient had also noticed bilateral loin pain during micturition. There was n o history of any serious disease in any patient. 4 of them had received antibacterial treatment, but sulphonamides, ampicillin, cephalosporins, nitrofurantoin and nalidixic acid had produced no improvement and the pyuria persisted. Most of the patients looked ill; 1 was admitted directly from Out-patients, a second shortly afterwards when his symptoms deteriorated, and a third as an emergency with increasing haematuria. All were apyrexial. 2 had suprapubic tenderness, and 2 had a tender prostate gland. 1 of the latter had a urethral discharge. The youngest patient was hypertensive, with a blood pressure of lSOjll.5 mm Hg. Repeated mid-stream specimens of urine showed pus and red blood cells, but there was no growth on culture, and repeated cultures for acid-fast bacilli were also negative. Haemoglobin estimations were all within normal limits and whte cell counts varied from 6,000 to 13,000 per mm3, with a normal differential count. In the most severe case the sedimentation rate was 13 rnm per hour. The serum creatinine and urea estimations were normal and there were no other abnormal biochemical findings. The intravenous urogram showed immediate renal function, with normal upper urinary tracts in 2 cases and bilateral clubbed calyces and dilated ureters in 3 cases (Fig. 1). The bladder outline in all the patients was small and irregular (Fig. 2). At cystoscopy the bladder capacity was much reduced and the mucosa intensely congested. The appearances were compatible with a diagnosis Read at the 33rd Annual Merting of the British Association of Urological Surgeons in Aberdeen, June 1977. 647
648
BRITISH JOURNAL OF UROLOGY
of vesical tuberculosis. Bimanual examination was normal with the prostate being reported normal in all cases. Biopsy of the bladder wall showed infiltration by acute and chronic inflammatory cells, including polymorphonuclear leucocytes, histiocytes and occasional lymphocytes, eosinophils and macrophages. In 1 case these changes were present in both bladder and prostatic biopsies. The 2 early cases seen in Portsmouth were not treated at first, as tuberculosis seemed the likely diagnosis, and only after a long series of urine tests proved negative was any other diagnosis suspected. The symptoms in 1 of these patients settled spontaneously, but in the other patient the symptoms persisted unchanged for 4 months. “Abacterial cystitis” was then suspected and treatment with tetracycline was instituted. His symptoms immediately improved. Other patients in the series were treated with tetracycline at a much earlier stage. A standard dosage of 250 mg 4 times daily proved quite sufficient. The blood and pus gradually disappeared from the urine and, in 2 patients, a follow-up intravenous urogram has shown much improved appearances. 3 patients have had a follow-up cystoscopy, one 3 months after treatment when normal appearances were reported, a second after 8 months because of a failing stream. There was
Fig. 1. Intravenous urogram showing typical appearances of small contracted bladder, dilated ureters and clubbed calices. Fig. 2. Intravenous urogram showing irregular contracted bladder with normal upper urinary tracts.
ABACTERIAL CYSTlTIS
649
a short bulbar stricture but the bladder was normal and the stricture settled after out-patient dilatation. A third case had a cystoscopy because of a recurrence of urethral discharge but the bladder appeared quite normal, as did the prostate. The subsequent progress for each patient has been relatively uncomplicated. 1 had perineal aching and pain after intercourse, with occasional urgency of micturition. He has attended the Eye Department with idiopathic retinal haemorrhages, and a diagnosis of Reiter’s disease was considered; however, his symptoms settled and no positive diagnosis was established. The most recent case, who was treated less than a year ago, is symptom free at present. His raised blood pressure on admission had settled at the time of his follow-up cystoscopy 3 months later. Discussion
This condition seems to be a disease of young male patients. Donovan (1946) in his cases described an associated sterile urethral discharge. Goldstein (1947) reported severe cystitis associated with Reiter’s Syndrome. Cultures of the urine in previous reports have never reliably established a cause although Coutts and Vargas-Zalazar (1946) found a spirilla in 5 cases and Czekalowski and Horne (1951) a spirochaete. The bladder seems to be principally affected. The 3 cases reported by Moore et al. (1971) all had normal upper urinary tracts, I patient was hypertensive. Hanky and Stept (1950) mentioned the value of tetracycline in this condition, and Moore et al. (1971) found organic arsenicals useful. The cause of the condition has yet to be established. Although it has been called “Abacterial cystitis” the evidence would suggest that it is an infective condition, in that there is pus and blood in the urine, the bladder mucosa is inflamed, and the symptoms respond to tetracycline. The response to tetracycline makes a viral aetiology unlikely, but the pathogen might be a mycoplasma or chlamydia which is sensitive to tetracycline but not to other commonly used antibacterials. Mycoplasma are known to cause cystitis (Berg, Weinberger and Dienes, 1957). These organisms were not sought either in urine or from urethral discharge in any of our patients. If the pathogen was a bacteria, however, it is possible that it was not detected by the standard culture methods used. Our patients’ mid-stream urines were cultured on MacConkey agar at the time they presented and it has been recognised since then that this medium does not reliably support the growth of Staphylococcus albus, one type of which, the micrococcus, is now known to be a cause of cystitis (Maskell, 1974). Furthermore, there are organisms known to be fastidious in various ways ; they may be slow growing and require a longer incubation time than is usually used, or they may be micro-aerophilic or even anaerobic. Since this problem was discussed with a bacteriologist, our laboratory has recorded 3 cases in which a mid-stream urine sent in by a general practitioner from a young male with acute urinary symptoms showed pyuria and haematuria, but again no organisms on culture by routine techniques. Cultures were repeated using other media and longer incubation, a micrococcus was isolated from one, a strain of Acinetobacter lwoflii from a second, and a coliform from a third. With hindsight, therefore, it is impossible to say that there were no bacteria in these patients’ urines. The diagnosis of “Abacterial cystitis” should not therefore be made until careful bacteriological investigations have been undertaken. In this way, the causative organism or organisms might be established. This condition has a close similarity to genito-urinary tuberculosis and should be remembered in any young male patient with a sterile pyuria in whom acid-fast bacilli cannot be cultured. Summary 5 young male patients with all the symptoms and signs of genito-urinary tuberculosis but in whom no organism could be cultured from the urine are described. 4 of them rapidly responded to a course of tetracycline. 4917-~
650
BRITISH JOURNAL OF UROLOGY
Various organisms are suggested as a cause of this condition, and careful bacteriological investigation in the future might discover the cause. I should like to thank the Surgeons of the Portsmouth and Southampton Districts for allowing me to publish their cases, and Dr R. Maskell of the Bacteriological Department, Saint Mary’s Hospital, Portsmouth, for her helpful advice. I should also like to thank Mr D. MacLean, Medical Photographer, Portsmouth District Hospitals, for his help in the preparation of the illustrations.
References BERG,R. L., WEINBERGER, H. and DIENES,L. (1957). Acute hemorrhagic cystitis, an infection associated with pleuropneumonia-like organisms and related to urethritis and prostatitis. American Journal of Medicine, 22, 848-864. COUTTS,W. E. and VARGAS-ZALAZAR, R. (1946). Abacterial pyuria with special reference to infection by spirochaetes. British Medical Journal, 2, 982-983. CZEKALOWSKI, J. W. and HORNE, G. 0. (1951). Abacterial cystitis: report of three cases and isolation of a spirochaete from one. British Medical Journal, 2, 879-881. DONOVAN, H. (1945). Abacterial pyuria. British Medical Journal, 2, 12-13. A. E. (1947). Reiter’s disease followed by true infective abacterial pyuria. British Journal of Uro/ogy, 19, GOLDSTEIN, 32-34. HANKEY, S . M. and STEPT,R. (1950). Abacterial pyuria, response to aureomycin. Journal of Urology, 63, 912-914. MASKELL, R. (1974). Importance of coagulase-negative staphylococci as pathogens in the urinary tract. Lancet, 1, 1155-1158. MOORE, T. (1940). Sterile pyuria. Proceedings of the Royal Society of Medicine, 33, 593-599. T., PARKER, C. and EDWARDS, E. C. (1971). Sterile non-tuberculous pyuria. British Journal of Urology, 43, MOORE, 47-51.
The Authors P. T. Doyle, FRCS, Senior Registrar, Department of Urology, St. Mary’s General Hospital, Portsmouth. G. F. Abercrombie, FRCS, Consultant Urological Surgeon, Portsmouth and S.E. Hants. Health District. J. D. Jenkins, MChir, FRCS, Consultant Urological Surgeon, Southampton University Hospitals. C. J. Smart, FRCS, Consultant Urologist, Southampton and S.W. Hants. Health District. J. Vinnicombe, MChir, FRCS, Consultant Urological Surgeon, Portsmouth Hospitals Group.
