Painful bladder syndrome interstitial cystitis

Pathophysiology/epidemiology

Painful bladder syndrome (PBS; alternatively known as bladder pain syndrome) is a descriptive diagnosis that has been recently advocated for use on an international level as descriptive of a complex of urologic complaints including pain [59]. Thought to be an early form of the disorder interstitial cystitis (IC), there is an expectation that a majority of patients with PBS might have a common etiology. Notably, IC has no agreed etiology, pathophysiology or treatment and nor does the less defined PBS. The prevalence of IC is estimated to be 2 in 10,000 with a female to male ratio of 10:1. Patients with IC are 10-12 times more likely to report childhood bladder problems than the general population [60]. IC is frequently associated with other chronic disorders such as inflammatory bowel disease, systemic lupus erythematosus, irritable bowel syndrome, "sensitive" skin, fibromyalgia and allergies [61].

Interstitial cystitis does have a defining pathology in that the diagnosis, as defined by a study group of the United States National Institute of Diabetes, Digestive and Kidney Diseases, requires the presence of mucosal ulcers (a Hunner's patch) or "glomeru-lations." The latter are small submucosal petechial hemorrhages viewed cystoscopically after sustained distension of the bladder (hydrodistension). Glomerulations are not unique to IC but occur in other forms of cystitis (e.g. radiation cystitis) and may even be a normal variant. As a consequence, the formal diagnosis of IC also requires exclusion of known disorders which produce pain and/or glomerulations (e.g. viral infection, chemotherapy exposure).

There is good evidence that there is a disruption of the normal urothelial barrier in most if not all IC patients. The etiology of the breakdown in the urothelial barrier and the consequences of this breakdown in IC are, as yet, unknown. One theory proposes that the breakdown of the urothelial barrier results from a failure to maintain adequate formation of glycosaminoglycans, the protective coating of the urothelium. Another theory proposes that IC is a systemic autoimmune disease presenting as a local manifestation with associated immunologic dysfunction, including possible abnormal mast cell activity. The most mechanistic theory to date relates the breakdown of the urothelial barrier to the presence of a specific peptide present within the urine of IC patients that impairs urothelial regrowth. Named the antiproliferative factor (APF), this low molecular weight peptide is a member of the Frizzled 8 protein family [62]. APF has been identified in over 90% of rigorously diagnosed IC patients and, at present, is the best laboratory diagnostic test for IC. Unfortunately, it is currently only available as a research tool. Whether APF is present due to developmental, immunologic, infectious, genetic or neurologic causes has not been determined. It has been demonstrated to produce a downregulation of genes which stimulate epithelial proliferation and an upregulation of genes that inhibit cell growth. Independent of the specific reason for urothelial disruption, the simplest explanation of the consequences of this breakdown is that it allows an exposure of urinary constituents, bacterial products and cell death products to bladder sensory nerves that normally are protected by an intact urothelial barrier. "Toxic" urine exposure may then produce either direct activation or sensitization of peripheral and/or central nervous system structures. It is likely that all these theories are correct for subsets of patients and that multiple different pathophysiolo-gies are being grouped together under one diagnosis.

Evaluation/treatment

Pain, nocturia, urgency and frequency are the primary symptoms of IC. Pain may be localized to the lower abdomen, pelvis, groin and/or perineum [60]. The onset of the disease may follow an "event" but is notable for a rapid progression of symptomatology. Depression and anxiety are frequent co-morbidities. In one analysis, Clemens and associates reported that 25% of patients with IC also carried an International Statistical Classification of Diseases (ICD)-9 diagnosis of depressive disorder and 19% carried a diagnosis of anxiety. In this study, compared to controls, patients with IC were also more likely to suffer from fibro-myalgia, gastritis, headaches, esophageal reflux and back pain, and were more likely to have a history of child abuse [63]. Suprapubic tenderness to palpation may accompany a diagnosis of IC. Although a history of frequent urinary tract infections is twice as common in IC patients as in non-IC patients, most report infrequent urinary tract infections (<1/year) prior to the onset of their symptoms, and they typically have sterile urine on laboratory exam. A cysto-scopic examination of the bladder wall is necessary to meet the research definition of IC (Hunner's patch or glomerulations needed). The intravesical potassium sensitivity test has been employed as an alternative diagnostic procedure with good sensitivity (70-90%) for subjects meeting formal research criteria, but it lacks specificity [64].

The ultimate goal of therapy is to neutralize the factor or factors responsible for a disease process. In the absence of any known causative factors, the treatments for IC have been guided by theory and/or prudence. A given patient's therapy typically progresses from the least invasive treatments to the more invasive. A list of potential treatments for IC is given in Box 15.5. While there are no universally accepted treatments, most patients are initially treated with oral medications such as NSAIDs, antihista-mines, antidepressants or cyclosporine, among others [65]. These are based on varying degrees of evidence as outlined in the box. A comparison of cyclosporine to pentosan polysulfate has found cyclosporine to be more effective in reducing urinary frequency with a response rate of 75% for cyclosporine versus 19% for pentosan polysulfate [66, 67]. More invasive treatments such as electrical nerve stimulation, nerve blocks or surgical resection may be required in some patients [65, 68].

Epidemiologically, IC is most prevalent in young to middle-aged women, implying there may be a

Beat Depression Now

Beat Depression Now

Let me be up front. My intention is to sell you something. Normally, it's not wise to come out and say that. However, I can do so because I have such an incredible deal for you that you'd be crazy to pass on it.

Get My Free Ebook


Post a comment