World J Urol (1993) 11:178- 182 Free paper 1 World Journal of ~' Urology © Springer-Verlag 1993 Clinical experience with multiagent intravesical therapy in interstitial cystitis patients unresponsive to single-agent therapy G.M. Ghoniem, D. McBride, O.P. Sood, and V. Lewis Department of Urology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA Summary. A total of 25 patients with the diagnosis of in- terstitial cystitis (IC) were involved in this study. All pa- tients had been previously diagnosed with interstitial cystitis and had received treatment with single intravesical agents. Patients were divided into two groups according to their bladder capacity. The bladder capacity was >350 ml in group I patients and <350 ml in group II patients. For our study, dimethylsulfoxide (DMSO), methylprednisolone, and heparin sulfate were given every week for a total of 6 weeks. When symptoms recurred, supportive oral pharmacotherapy consisting of an- ticholinergics and/or tricyclic antidepressants was given. Under anesthesia, patients in group I showed a 99% in- crease in their bladder capacity; whereas those in group II showed an increase of only 19%. Cystoscopically, Hunner's ulcers were present in 60°7o of the group II pa- tients but were seen in only 5% of the group I patients. Histopathological examination showed that the inflam- matory changes were more frequent and severe in group II than in group I. Mast-cell hyperplasia was present in 100% of the patients in group II, versus only 61% of those in group I. A total of 23 patients (92%) achieved an initial remission averaging 8.1 months. In all, 9 pa- tients (35°7o) had 1 or more relapses, and all achieved a subsequent remission averaging 8 months. By this com- bined multiagent approach, the majority of patients with IC obtained relief from their incapacitating symptoms and were socially rehabilitated. Few diseases prove as difficult to diagnose and as difficult to treat as interstitial cystitis (IC). Afflicted patients suf- fer from incapacitating urgency, frequency, nocturia, and pain. Quality-of-life scores measured in these patients Correspondence to GM. Ghoniem, M.D., EA.C.S. have been lower than those recorded for patients with chronic renal disease [1]. Patients are understandably frustrated when told they have a disease of unknown eti- ology, a disease with no cure. Since the exact etiology and a specific cure are as yet unknown, we developed a proto- col that uses intravesical multiagent therapy supplement- ed by oral medications as needed. An essential part of the program is a group of supportive compassionate person- nel, incuding physicians and nurses who can translate their own confidence into optimism and hope for these desperate patients. The problems of IC in women are estimated to occur in between 18 and 36 per 100,000. The female-to-male ra- tio is 10 to 1 and the average age at diagnosis is between 40 and 50 years [2]. Very few blacks have been diagnosed with IC. The average interval from the onset of symptoms to diagnosis has been 24-51 months; this interval has re- cently been reduced due to more awareness of physicians and patients with the disease. Although the majority of patients are middle-aged and white women, both children and the elderly may be afflicted. Several etiological theo- ries have been proposed. Among those that have been ex- plored are infections [3, 4], exposure to toxic substances in the urine [5], autoimmune disease [6-11], hypersensi- tivity reaction to local stimulants [12, 13], neurogenic or vascular inflammation [14-18], and psychosomatic ori- gin [19, 20]. Despite much research, the etiology remains elusive. Considerable attention has focused on the possi- bility that the protective glycosaminoglycan (GAG) lining the transitional epithelium leaks, allowing toxic substanc- es to penetrate the deeper layers and induce an inflamma- tory response [21- 23]. Nonetheless, the reported success of heparin-like agents seems logically based on their abil- ity to simulate this GAG-defense layer [24, 25]. Addition- ally, the success of the time-tested dimethylsulfoxide (DMSO) in the treatment of IC probably lies in its anti- inflammatory properties. Our goal in this study was to evaluate multiagent in- travesical therapy to induce remission of the disease in patients who did not respond to previous single-agent therapy.