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THE INCIDENCE OF HELICOBACTER PYLORI IN PATIENTS WITH INTERSTITIAL CYSTITIS
00225347/98/1593-0772$03.00/0
Vol. 159,772-773, March 1998 Printed in U.S.A.
Tm:JOURNAL OF UROUJCY Copyright 8 1998 by AMERICAN U R O ~ I C ASSOCIATION, AL INC.
THE INCIDENCE OF HELICOBACTER PYLORI IN PATIENTS WITH INTERSTITIAL CYSTITIS SHARON F. ENGLISH, MONICA LIEBERT, CINDY A. CROSS
AND
EDWARD J. McGUIRE
From the Departments of Urology, and Obstetrics and Gynecology, M . D. Anderson Cancer Center, University of Texas, Houston Texas
ABSTRACT
Purpose: The cause of interstitial cystitis is unknown. We evaluated the incidence of Helicobacter pylori antibodies in patients with interstitial cystitis to determine whether such infection may be a causative factor. Materials and Methods: We obtained serum samples from 23 patients with interstitial cystitis and 23 control subjects. Samples were analyzed for the presence of H. pylori IgG antibodies. Results: The incidence of positive tests for H. pylon antibodies was 22% in the interstitial cystitis group and 35% in controls. Conclusions: The incidence of infection with H. pylori is not increased in interstitial cystitis, and so it is unlikely to be a causative factor. KEYWORDS:bladder, urination disorders, pain
Interstitial cystitis is a chronic bladder disease characterized by severe urinary symptoms. Intractable pain with bladder filling causes daytime and nighttime urinary frequency. It is estimated that there are 20,000 to 90,000 diagnosed cases of interstitial cystitis in the United States, although the estimate of undiagnosed cases is 4 to 5 times that number.' A tenth of these patients are men? The etiology of interstitial cystitis is unknown but several features suggest that it may be an infectious disease. The predominance of women with the syndrome, frequently acute onset of symptoms, inflammatory changes on histopathological evaluation and presence of IgA deposits in bladder epithelium suggest that the condition may be caused by an infective However, to our knowledge no microorganism as been incriminated as a cause of interstitial cystitis. Recently a patient reported that interstitial cystitis symptoms improved dramatically after treatment for Helicobacter pylon infection. We decided to perform a controlled study to determine the incidence of H. pylori antibodies in women with interstitial cystitis. If the incidence were much higher than that in the normal population, we could propose that H. pylon may have a role in the development of interstitial cystitis.
was obtained and sent to the laboratory to test for H. pylon antibodies using an enzyme-linked immunosorbent assay. To accept H. pylon as a cause for interstitial cystitis positive results should be present in at least 95% of the study population. Because 11to 24% of the normal United States population are positive for H. pylon antibodies by this test, 21 participants were needed in each of the control and study groups to achieve 80% power with significance at p = 0.05. Results were analyzed using the 2-sided chi-square test. RESULTS
At the time of this study all patients with interstitial cystitis fulfilled National Institute of Diabetes and Digestive and Kidney Diseases criteria.' Tests in 5 of the 23 patients with interstitial cystitis and 8 controls were positive for H. pylon IgG antibodies. Using the 2-sided chi-square test there was no statistical difference between the 2 groups (p = 0.5125, see table). DISCUSSION
Hunner was among the first to suggest chronic bacterial infection as the underlying causative factor in the develop.~ microorganisms have ment of interstitial ~ y s t i t i sVarious been reported in the literature that support an infective agent in interstitial cystitis. The study of Domingue et al MATERIALS AND METHODS using the polymerase chain reaction demonstrated bacterial Women with interstitial cystitis were contacted at a local deoxyribonucleicacid in bladder biopsies from patients with meeting of the Interstitial Cystitis Association, and 23 interstitial cystitis.' Ratliff et a1 showed that many fastidious women, average age 53.3 years with a 2 to 38-year (mean 11) microorganisms are not detected by conventional culture history of symptoms, were enrolled in the study. In 10 patients (43%) symptoms had been relieved with antibiotics. techniques, and require special culture medium and prolonged incubation in a particular environment for identificaThree patients had received long-term antibiotics but the t i ~ n . ~ medications were discontinued after a few years when they H. pylori is a unipolar multiflagellate microorganism that failed to provide relief. In the remaining 7 cases antibiotics were administered only when a urinary tract infection was is recognized as a cause of gastric ulceration and malignancies, and acne rosacea. Approximately 11 to 24% of the documented. A total of 23 women with a mean age of 49.4 years who were relatives of patients attending the urology clinic were acquired as controls. f i r informed consent was Results of testing serum for H. Dvlori antibodies obtained participants were asked to complete a questionnaire based on the National Institutes of Health criteria for incluNo. Pts. (%) Total No. sion of patients with interstitial cystitis into studies.' Blood Interstitial cystitis group Accepted for publication August 22, 1997. Control group Supported by a grant from the Women's Fund for Health Education and Research, Houston, Texas. p = 0.5125. 772
Pos.
Nea.
5 (22)
18 (78) 15 (65)
8 (35)
23 23
HELICOBACTER PYLORI IN INTERSTITIAL CYSTITIS
773
United States population are seropositive for H. l1 However, only a minority have symptoms of gastric or skin infection. Isogai et a1 introduced H. pylon into the bladders of mice, causing an intense inflammatory reaction, but they did not evaluate the long-term effect of H. pylori on the bladder." Keay et a1 obtained samples from 11 patients with interstitial cystitis and tried unsuccessfully to culture them for H. pylori using chocolate agar plates in a microaerophilic environment at 35C.13 They observed culture growth of a number of other fastidious organisms in 67% of the cases that would not have been cultured using normal laboratory techniques.
rescent and histochemical staining confirm the identification of the many diseases called interstitial cystitis. Brit. J. Urol., 68:265,1990. 4. Said, J. W., Van de Velde, R. and Gillespie, L.: Immunopathology of interstitial cystitis. Mod. Path., 2 593, 1989. 5. Marsh, F.P., Banerjee, R. and Panchamia, P.: The relationship between urinary infection, cystoscopic appearance, and pathology of the bladder of man. J. Clin. Path., 27:297, 1974. 6. Fukushi, Y. and Orisaka, S.: The role of intravesical polymorphonuclear leukocytes in experimental cystitis. Invest. Urol.,
CONCLUSIONS
Human, L. G.: Dormant microbes in interstitial cystitis. J. Urol., 153: 1321,. 1995. 9. Ratliff, T. L., Klutke, C. G. and McDougall, E. M.: The etiology of interstitial cystitis. Urol. C h . N. Amer., 21: 21, 1994. 10. Goh, K. L., Parasakthi, N. and Ong, K. K: Prevalence of Helicobacter pylon infection in endoscopy and nonendoscopy personnel results of field survey with serology and 14C-urea breath test. h e r . J. Gastmenterol., 91: 268, 1996. 11. Smoak, B. L., Kelley, P. W. and Taylor, D. N.: Seroprevalence of Helicobacter pylori infections in a cohort of US A r m y recruits. Amer. J. Epidemiol., 139: 513, 1994. 12. Isogai, H., Isogai, E., Kimura, K., Fujuii, N., Yokota, K. and Oguma, K.: Helicobacter pylon induces inflammation in mouse urinary bladder and pelvis. Microbiol. Immunol., 38.
Our prospective controlled study provides no evidence that interstitial cystitis is only the result of an infection by H. pylori. Patients with interstitial cystitis had the same incidence of H. pylori infection as controls. There is evidence to suggest that infectious agents, such as bacteria, may have a role in development of interstitial cystitis but no specific agent has yet been identified. REFERENCES
1. Gillenwater, J. Y. and Wein, A. J.: Summary of the National
Institute of Arthritis, Diabetes, Digestive and Kidney Diseases workshop on interstitial cystitis, National Institutes of Health, Bethesda, Maryland, August 28-29, 1987. J. Urol., 140 203, 1988.
2. Hanno, P. M., Staskin, D. R., Krane, R. J. and Wein, A. J.: Interstitial Cystitis, London: Springer-Verlag, 1990. 3. Gillespie, L., Said, J., Sostrin, S. and Kleiwer, K.: Immunofluo-
18 471, 1981. 7. Hunner, G.: Elusive ulcer of the bladder. Amer. J. Obst., 7 8 374, 1918. 8. Domingue, G. J., Ghoneim, G. M., Bost, K. L., Fermin, C. and
331, 1994. 13. Keay, S., Schwalbe, R. S.,Trifills, A. L., Lovchik, J. C., Jacobs, S.
and Warren, J. W.: A prospective study of microorganisms in urine and bladder biopsies from interstitial cystitis patients and controls. Urology, 45.223, 1995.
Vol. 159,772-773, March 1998 Printed in U.S.A.
Tm:JOURNAL OF UROUJCY Copyright 8 1998 by AMERICAN U R O ~ I C ASSOCIATION, AL INC.
THE INCIDENCE OF HELICOBACTER PYLORI IN PATIENTS WITH INTERSTITIAL CYSTITIS SHARON F. ENGLISH, MONICA LIEBERT, CINDY A. CROSS
AND
EDWARD J. McGUIRE
From the Departments of Urology, and Obstetrics and Gynecology, M . D. Anderson Cancer Center, University of Texas, Houston Texas
ABSTRACT
Purpose: The cause of interstitial cystitis is unknown. We evaluated the incidence of Helicobacter pylori antibodies in patients with interstitial cystitis to determine whether such infection may be a causative factor. Materials and Methods: We obtained serum samples from 23 patients with interstitial cystitis and 23 control subjects. Samples were analyzed for the presence of H. pylori IgG antibodies. Results: The incidence of positive tests for H. pylon antibodies was 22% in the interstitial cystitis group and 35% in controls. Conclusions: The incidence of infection with H. pylori is not increased in interstitial cystitis, and so it is unlikely to be a causative factor. KEYWORDS:bladder, urination disorders, pain
Interstitial cystitis is a chronic bladder disease characterized by severe urinary symptoms. Intractable pain with bladder filling causes daytime and nighttime urinary frequency. It is estimated that there are 20,000 to 90,000 diagnosed cases of interstitial cystitis in the United States, although the estimate of undiagnosed cases is 4 to 5 times that number.' A tenth of these patients are men? The etiology of interstitial cystitis is unknown but several features suggest that it may be an infectious disease. The predominance of women with the syndrome, frequently acute onset of symptoms, inflammatory changes on histopathological evaluation and presence of IgA deposits in bladder epithelium suggest that the condition may be caused by an infective However, to our knowledge no microorganism as been incriminated as a cause of interstitial cystitis. Recently a patient reported that interstitial cystitis symptoms improved dramatically after treatment for Helicobacter pylon infection. We decided to perform a controlled study to determine the incidence of H. pylori antibodies in women with interstitial cystitis. If the incidence were much higher than that in the normal population, we could propose that H. pylon may have a role in the development of interstitial cystitis.
was obtained and sent to the laboratory to test for H. pylon antibodies using an enzyme-linked immunosorbent assay. To accept H. pylon as a cause for interstitial cystitis positive results should be present in at least 95% of the study population. Because 11to 24% of the normal United States population are positive for H. pylon antibodies by this test, 21 participants were needed in each of the control and study groups to achieve 80% power with significance at p = 0.05. Results were analyzed using the 2-sided chi-square test. RESULTS
At the time of this study all patients with interstitial cystitis fulfilled National Institute of Diabetes and Digestive and Kidney Diseases criteria.' Tests in 5 of the 23 patients with interstitial cystitis and 8 controls were positive for H. pylon IgG antibodies. Using the 2-sided chi-square test there was no statistical difference between the 2 groups (p = 0.5125, see table). DISCUSSION
Hunner was among the first to suggest chronic bacterial infection as the underlying causative factor in the develop.~ microorganisms have ment of interstitial ~ y s t i t i sVarious been reported in the literature that support an infective agent in interstitial cystitis. The study of Domingue et al MATERIALS AND METHODS using the polymerase chain reaction demonstrated bacterial Women with interstitial cystitis were contacted at a local deoxyribonucleicacid in bladder biopsies from patients with meeting of the Interstitial Cystitis Association, and 23 interstitial cystitis.' Ratliff et a1 showed that many fastidious women, average age 53.3 years with a 2 to 38-year (mean 11) microorganisms are not detected by conventional culture history of symptoms, were enrolled in the study. In 10 patients (43%) symptoms had been relieved with antibiotics. techniques, and require special culture medium and prolonged incubation in a particular environment for identificaThree patients had received long-term antibiotics but the t i ~ n . ~ medications were discontinued after a few years when they H. pylori is a unipolar multiflagellate microorganism that failed to provide relief. In the remaining 7 cases antibiotics were administered only when a urinary tract infection was is recognized as a cause of gastric ulceration and malignancies, and acne rosacea. Approximately 11 to 24% of the documented. A total of 23 women with a mean age of 49.4 years who were relatives of patients attending the urology clinic were acquired as controls. f i r informed consent was Results of testing serum for H. Dvlori antibodies obtained participants were asked to complete a questionnaire based on the National Institutes of Health criteria for incluNo. Pts. (%) Total No. sion of patients with interstitial cystitis into studies.' Blood Interstitial cystitis group Accepted for publication August 22, 1997. Control group Supported by a grant from the Women's Fund for Health Education and Research, Houston, Texas. p = 0.5125. 772
Pos.
Nea.
5 (22)
18 (78) 15 (65)
8 (35)
23 23
HELICOBACTER PYLORI IN INTERSTITIAL CYSTITIS
773
United States population are seropositive for H. l1 However, only a minority have symptoms of gastric or skin infection. Isogai et a1 introduced H. pylon into the bladders of mice, causing an intense inflammatory reaction, but they did not evaluate the long-term effect of H. pylori on the bladder." Keay et a1 obtained samples from 11 patients with interstitial cystitis and tried unsuccessfully to culture them for H. pylori using chocolate agar plates in a microaerophilic environment at 35C.13 They observed culture growth of a number of other fastidious organisms in 67% of the cases that would not have been cultured using normal laboratory techniques.
rescent and histochemical staining confirm the identification of the many diseases called interstitial cystitis. Brit. J. Urol., 68:265,1990. 4. Said, J. W., Van de Velde, R. and Gillespie, L.: Immunopathology of interstitial cystitis. Mod. Path., 2 593, 1989. 5. Marsh, F.P., Banerjee, R. and Panchamia, P.: The relationship between urinary infection, cystoscopic appearance, and pathology of the bladder of man. J. Clin. Path., 27:297, 1974. 6. Fukushi, Y. and Orisaka, S.: The role of intravesical polymorphonuclear leukocytes in experimental cystitis. Invest. Urol.,
CONCLUSIONS
Human, L. G.: Dormant microbes in interstitial cystitis. J. Urol., 153: 1321,. 1995. 9. Ratliff, T. L., Klutke, C. G. and McDougall, E. M.: The etiology of interstitial cystitis. Urol. C h . N. Amer., 21: 21, 1994. 10. Goh, K. L., Parasakthi, N. and Ong, K. K: Prevalence of Helicobacter pylon infection in endoscopy and nonendoscopy personnel results of field survey with serology and 14C-urea breath test. h e r . J. Gastmenterol., 91: 268, 1996. 11. Smoak, B. L., Kelley, P. W. and Taylor, D. N.: Seroprevalence of Helicobacter pylori infections in a cohort of US A r m y recruits. Amer. J. Epidemiol., 139: 513, 1994. 12. Isogai, H., Isogai, E., Kimura, K., Fujuii, N., Yokota, K. and Oguma, K.: Helicobacter pylon induces inflammation in mouse urinary bladder and pelvis. Microbiol. Immunol., 38.
Our prospective controlled study provides no evidence that interstitial cystitis is only the result of an infection by H. pylori. Patients with interstitial cystitis had the same incidence of H. pylori infection as controls. There is evidence to suggest that infectious agents, such as bacteria, may have a role in development of interstitial cystitis but no specific agent has yet been identified. REFERENCES
1. Gillenwater, J. Y. and Wein, A. J.: Summary of the National
Institute of Arthritis, Diabetes, Digestive and Kidney Diseases workshop on interstitial cystitis, National Institutes of Health, Bethesda, Maryland, August 28-29, 1987. J. Urol., 140 203, 1988.
2. Hanno, P. M., Staskin, D. R., Krane, R. J. and Wein, A. J.: Interstitial Cystitis, London: Springer-Verlag, 1990. 3. Gillespie, L., Said, J., Sostrin, S. and Kleiwer, K.: Immunofluo-
18 471, 1981. 7. Hunner, G.: Elusive ulcer of the bladder. Amer. J. Obst., 7 8 374, 1918. 8. Domingue, G. J., Ghoneim, G. M., Bost, K. L., Fermin, C. and
331, 1994. 13. Keay, S., Schwalbe, R. S.,Trifills, A. L., Lovchik, J. C., Jacobs, S.
and Warren, J. W.: A prospective study of microorganisms in urine and bladder biopsies from interstitial cystitis patients and controls. Urology, 45.223, 1995.