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Bladder Pain syndrome/Interstitial cystitis

Interstitial cystitis (IC) is a chronic noninfectious inflammatory condition characterized by a wide spectrum of clinical presentations ranging from pelvic pain along with irritative lower urinary tract symptoms with or without evidence of hematuria. It is an uncommon clinical condition presenting as painful bladder syndrome, is often missed leading to avoidable complications and undue suffering. Pain is usually felt more on full bladder and subsides after urination. There is a suggestion that men with non-bacterial prostatitis might actually represent apart of spectrum of clinical presentation of Interstitial Cystitis. (1) Since it is primarily a diagnosis of exclusion, it is essential to exclude other conditions, which mimic IC. There are two varieties of IC, the classic and non-ulcerative. Presently there is no evidence to suggest that non-ulcerative variety may progress to ulcerative variety(2)

Various theories have been put forward to explain the etiopathology of this condition but they are individually incomplete. It has been postulated that infection with non-culturable organism is responsible for this condition.(3)1 In 1994; Mansoury(4)2 demonstrated increased levels of methyl histamine in urine samples of patients with IC, which may be as a result of mast cell infiltration. Hence, it was considered as an allergic condition. Defective epithelial permeability due to lack of surface glycosaminoglycans (GAG) is considered as one of the responsible factors.(5)3 This increased permeability causes back diffusion of urea and other solutes into sub epithelial layer leading to pancystitis(6).4 Akiyama (2000), Stein (1990), Peeker (1998), Bade (1996), Buffington (1996) and many other have demonstrated various urinary abnormalities responsible for chronic inflammatory state of entire bladder wall leading to interstitial cystitis(7-11).5-9 Harrington(12)10 demonstrated sheets of plasma cells, aggregates of T cells and B cells nodules in biopsy obtained from bladder wall suggestive of autoimmune phenomenon as a causative factor of interstitial cystitis. Stress is also considered as one of the contributory factors as many of these patients are associated with psychological disturbances. Since this condition is commonly seen in females, hormonal factors have been considered as responsible for IC. Theories of neurogenic inflammation have been applied to explain the perpetuation of pain inflammation cycle(13).11

Literature is abound with various treatment options including oral agents like Nonsteroidal anti inflammatory drugs, narcotics, antihistamines, Pentosan polysulfate, tricyclic antidepressants, Gabapentin,and immunosuppressive agents. Hydrodistention and intravesical instillations of DMSO, (ref 14-b) BCG (ref15- c), Resiniferatoxin (ref16- d) have been reported to have beneficial effects ov various degrees and duration. DMSO is the only FDA approved intravesical agent for treatment of Interstitial cystitis (ref 17-e). DMSO has been shown to deplete substance P in the bladder urothelium and cause degranulation of mast cells (ref18- f) Even though earlier studies showed promising results with intravesical DMSO, later trials have had mixed conclusions about it’s efficacy. In 1998,Perez Marrero et al showed immediate response in unto 93% of patients, there was a high relapse rate in next 4 weeks (ref14- b). In a later study the same group demonstrated that addition of heparin caused longer periods of remission (ref19- g).

Heparinoids (Heparin, Pentosan polysulfate) have been shown to down regulate the sensory nerve endings by gradually restoring the barrier function of urothelium.(20)13 In addition to this; hydrocortisone may be added to reduce the already present inflammatory response in submucosal layer. Since the urothelial barrier is anyway weak in cases of IC, it is but logical to use intravesical route for hydrocortisone. Based on this we conducted this study to test the clinical efficacy of intravesical solution of hydrocortisone and heparin along with systemic agents in the treatment of 26 cases of interstitial cystitis.