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The investigation and management of interstitial cystitis.

Interstitial cystitis (IC) is a chronic inflammatory disorder of the bladder that is notoriously difficult to manage and can result in considerable morbidity. It very likely overlaps with painful bladder syndrome, but they are different conditions. The aetiology remains obscure, and the definition and diagnostic criteria are debated. The diagnosis of IC is one of exclusion, frequently based on symptoms and cystoscopy findings. Typical symptoms include frequency, urgency, dysuria and lower abdominal, bladder, vaginal, urethral or perineal pain, in the absence of bacterial cystitis. Voiding often relieves the suprapubic discomfort, and drinking alcohol- and caffeine-containing drinks frequently exacerbates it. Many treatments have been tried, with little sustained success. Proposed systemic treatments include anti-histamines, heparin, amitriptyline and pentosan polysulfate (a synthetic analogue of glycosaminoglycan which augments the mucous protective layer of the bladder). In many patients symptoms are improved following cysto-distension but the benefits are short-lived. Instillations of dimethyl sulfoxide, hyaluronic acid or chondroitin also show promise. Where treatments have failed and symptom severity is such that the patient's quality of life is poor, a urological opinion should be sought and reconstructive surgery considered. Available options include partial cystectomy, augmentation cystoplasty, and urinary diversion with or without cystectomy.

Analgesics, Non-Narcotic↗

New agents for the medical treatment of interstitial cystitis.

Interstitial cystitis (IC) is a painful, sterile, disorder of the urinary bladder characterised by urgency, frequency, nocturia and pain. IC occurs primarily in women but also in men with recent findings indicating that chronic, abacterial prostatitis may be a variant of this condition. The prevalence of IC has ranged from about 8 - 60 cases/100,000 female patients depending on the population evaluated. About 10% of patients have severe symptoms that are associated with Hunner's ulcers on bladder biopsy; the rest could be grouped in those with or without bladder inflammation. Symptoms of IC are exacerbated by stress, certain foods and ovulatory hormones. Many patients also experience allergies, irritable bowel syndrome (IBS) and migraines. There have been various reports indicating dysfunction of the bladder glycosaminoglycan (GAG) protective layer and many publications showing a high number of activated bladder mast cells. Increasing evidence suggests that neurogenic inflammation and/or neuropathic pain is a major component of IC pathophysiology. Approved treatments so far include intravesical administration of dimethylsulphoxide (DMSO) or oral pentosanpolysulphate (PPS). New treatments focus on the combined use of drugs that modulate bladder sensory nerve stimulation (neurolytic agents), inhibit neurogenic activation of mast cells, or provide urothelial cytoprotection, together with new drugs with anti-inflammatory activity.

Analgesics↗

Current strategies for managing interstitial cystitis.

Interstitial cystitis is a relatively common disorder that can be treated successfully in the majority of cases. Symptoms can be effectively controlled, and disease pathophysiology addressed, using a multimodal medical regimen based on heparinoid therapy. As appropriate to the individual patient, heparinoid therapy is supplemented by oral medications aimed at reversing neural upregulation and controlling any allergies. A new and promising adjunct to the multimodal regimen is an intravesical therapeutic solution that combines pentosan polysulfate or heparin with lidocaine and sodium bicarbonate. Preliminary results indicate this therapeutic solution provides immediate temporary relief of symptoms.

Administration, Intravesical↗

Interstitial cystitis.

Interstitial cystitis (IC) is a serious debilitating disease often overlooked by medical and health professionals. This paper describes the elusive aetiology and the painful symptoms of IC and how it affects the patient's life. The author outlines the treatments available and offers guidelines for supporting patients with the disease.

Cystitis, Interstitial↗

[Interstitial cystitis].

Interstitial cystitis is a disease characterized by pain occurring as the urinary bladder is gradually filling up. Its pathophysiology is unknown. The cause could be either a membrane permeability disorder, a mast cell disturbance in the bladder wall, or an autoimmune process involving the bladder. The diagnosis is essentially clinical but endoscopies and biopsies are required to rule out vesical cancers. Treatments is difficult and based on a combination of sanitary and dietary regimens, as well as drugs administered orally or infused within the bladder. Surgical treatment must remain exceptional.

Adult↗

Urine autoantibodies in interstitial cystitis.

Interstitial cystitis is a chronic bladder disease with certain features that suggest autoimmunity may play a role in initiating or maintaining the disease process. We therefore determined whether immunoglobulin fractions from 14 IC patient and 19 control urine specimens bound in vitro to primary cultures of human bladder epithelial cells, as well as epithelial cells from a variety of other tissues. Urine autoantibodies that bound to normal human bladder epithelial cells were present in 8 of 14 IC specimens (from 6 of 9 IC patients) as compared to 3 of 23 control specimens (from 2 of 17 control patients). These antibodies, which were usually also present at low titers in sera from these persons, bound to at least four nuclear or cytoplasmic antigens, with the specificity of autoantibodies from a given individual varying over time. The autoantibodies were not specific for normal or malignant bladder epithelial cells, but bound to epithelial cells from a variety of tissues. These data show that anti-epithelial cell autoantibodies are present in the urine of IC patients, but suggest that these antibodies are not likely to be a primary cause of this disease.

Adult↗

[Interstitial cystitis].

Interstitial cystitis (IC) is a complex of painful mictional symptomatology of unknown etiology. Is occurs more frequently in women. By cystoscopy the ulcerative and non-ulcerative form is differentiated. A typical diagnosis symptom are glomerulations during cystoscopy under general anaesthesia. There are diagnostic criteria which rule out IC. Histopathologically the following are differentiated: classical IC with proliferation of mastocytes in the detrusor, detrusor myopathy and eosinophil cystitis. Treatment includes intervesical instillation of various substances, transurethral procedures or supratrifonal cystectomy, incl. enterocystoplasty.

Adult↗

Modified urodynamics for interstitial cystitis.

Interstitial cystitis (IC) is a poorly understood syndrome. Patients with pelvic pain, urgency, frequency, and/or dysuria may pose a diagnostic dilemma. They may have bladder-related symptoms or they may have nonbladder related symptoms. It is beneficial for the urologist to distinguish between these patients. This study outlined a modified urodynamics test to discriminate between bladder-related and nonbladder-related patients. Consecutive IC patients (bladder-related and nonbladder-related patients) and stress incontinent controls underwent modified urodynamics. Testing consisted of an epithelial leak test, a filling cystometrogram, bladder emptying and instilling lidocaine intravesically, and repeat cystometrogram after bladder emptying. The epithelial leak test and lidocaine test predict reliably if a patient has bladder-related or nonbladder-related symptoms. Modified urodynamics permits a logical stratification of IC patients, and may predict treatment response.

Adult↗

Caring for the patient with interstitial cystitis.

Interstitial cystitis (IC) is a chronic, painful, debilitating bladder disorder which predominantly affects women. The etiology of IC is unknown, the diagnosis is difficult to make, and treatments are aimed at minimizing symptoms. IC affects every aspect of an individual's life. Both generalist and advanced practice nurses play a vital role in enhancing the IC patient's quality of life through emotional support and education.

Adult↗

Autoantibodies and interstitial cystitis.

Interstitial cystitis (IC) is a chronic inflammatory disease of the bladder characterized by symptoms of urgency, frequency, and pain. The etiology of IC is unknown but autoimmune mechanisms may play a causal or excerbating role since we have found that up to 50% of the IC patient population have autoantibodies, some of which are novel and others of which are shared by other diseases. We are currently investigating the role of autoantibody testing in relationship to diagnosis, prognosis and therapy of IC.

Autoantibodies↗

[Interstitial cystitis].

Interstitial cystitis is a particular type of cystitis with clear urine, essentially observed in women. Persistent painful urinary frequency and bladder heaviness are suggestive of the diagnosis. Two different forms have been distinguished according to severity: Hunner's ulcer and small capacity bladder;-bladder distension to 800 ml, followed by haemorrhagic petechiae; with a whole series of intermediate forms. The bladder wall undergoes inflammatory reorganization, without infection, leading to fibrosis. The disease is improved by hydrocortisone instillations. Hunner's ulcer can be treated by partial resection. If the cystitis deteriorates, bladder replacement by detubulized intestinal graft may be required.

Administration, Topical↗

Lymphocyte sub-populations in the bladder wall in normal bladder, bacterial cystitis and interstitial cystitis.

OBJECTIVE: To identify lymphocyte sub-populations within the bladder wall in normal controls, in patients with bacterial cystitis (BC) or interstitial cystitis (IC). PATIENTS AND METHODS: Bladder biopsies were taken from 21 patients with IC, four with BC and five normal controls. Immunofluorescent staining of biopsies was performed using monoclonal antibodies to the T cell markers CD3, CD4, CD8, TCR delta 1, delta TCS1, beta F1 and IML. Plasma cells were identified using monoclonal antibodies to IgA, IgG and IgM. The location and numbers of cells were determined. Peripheral blood lymphocyte counts were also performed in each case. RESULTS: T cells (CD4+ and CD8+) were significantly more abundant within the bladder biopsies from patients with interstitial cystitis than in those from the normal controls, and were present within the urothelium and submucosa but not the detrusor. There was no difference between the numbers of T cells present in the biopsies from patients with interstitial cystitis and in those with bacterial cystitis. However, the presence of gamma delta T cells was significantly associated with interstitial cystitis. IgA+ and IgM+ plasma cells were located within the urothelium and submucosa but not the detrusor in patients with IC and the numbers present in these patients were significantly greater than in those with BC or the normal controls. The peripheral blood lymphocyte counts were not altered in any of the study cases. CONCLUSION: The increased numbers of CD4+, CD8+ and gamma delta cells as well as IgA+, IgG+ and IgM+ plasma cells within the urothelium and submucosa in patients with IC suggest that these cells play an active role in the pathogenesis of the disorder. The previously described abnormal urothelial expression of HLA-DR and hyperexpression of Class I molecules in patients with IC may enable these cells to cause destruction of the urothelium--the end stage of IC.

Adult↗

Inflammatory mediator profile in urine and bladder wash fluid of patients with interstitial cystitis.

Interstitial cystitis is a syndrome of urinary urgency, frequency and suprapubic pain. We investigated the role of inflammatory mediators in 96 patients with histories and symptoms consistent with interstitial cystitis, and 13 controls from The New York Hospital-Cornell Medical Center, University of Washington and University of California at San Diego. Patients were classified into either group A (meets all criteria of the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases for inclusion in research studies), group B (meets all of these criteria but without glomerulations) or an "other" group. A small number of group A patients had detectable interleukin-6 in the urine. Urinary concentrations of tumor necrosis factor, prostaglandins E2, D2 and F2 alpha, and thromboxane B2 were not different among either patient groups or controls. Urine specimens contained inhibitors of the bioactivity of interleukin-6 and tumor necrosis factors but no differences between patients or controls were found. No factors chemotactic for human neutrophils were detected in a small patient sample. Bladder wash fluid concentrations of prostaglandins E2, D2 and F2 alpha, and thromboxane were much lower than urinary levels. Bladder wash fluid interleukin-6 and tumor necrosis factor were not detectable. The results suggest that while a small subset of patients may have elevated levels of interleukin-6 the majority of patients do not appear to have elevated levels of inflammatory mediators in the urine or bladder wash fluid. Evaluation of patient bladder tissue may indicate changes not detectable in urine or bladder wash fluid. Alternatively, other etiologies must be considered in those patients.

Adult↗

Current investigations and treatment of interstitial cystitis.

Interstitial cystitis (IC) is a chronic condition characterized by a constellation of symptoms such as urinary frequency, nocturia, urinary urgency, suprapubic pressure, and bladder and pelvic pain. Since its original description, the etiology of the disorder has remained unknown despite intense investigations. The International Cystitis Association (ICA) and the National Institutes of Arthritis, Diabetes, Digestive and Kidney Diseases (NIDDK) have been instrumental in supporting the United States Interstitial Database (ICDB) and foster research to study the disorder. The NIDDK developed criteria to ensure that all groups of patients treated would be relatively comparable. However, many patients who would be clinically considered to have IC do not fulfill all the NIDDK criteria. Many clinical criteria for the diagnosis of IC, such as the presence of glomerulations and the intravesical potassium chloride test, are being challenged. The epidemiology of the disorder is not well established, but there are an estimated 700,000 cases of IC in the United States. Numerous pathophysiologic mechanisms have been proposed, but none have been proven. There is no representative animal model of IC. Both the oral and intravesical treatments of IC are noncurative, and few are based on a plausible mechanism or scientific evidence. Surgical treatment should be considered with extreme caution; it is the last therapeutic option because failure rate can be substantial.

Biomedical Research↗

Characteristics of mast cells in normal bladder, bacterial cystitis and interstitial cystitis.

An analysis was made of the numbers and characteristics of mast cells in lateral bladder wall biopsies from 22 patients with interstitial cystitis, 6 with bacterial cystitis and 8 normal controls, using toluidine blue stains and computerised video image analysis techniques. A significantly greater number of mast cells were found within the detrusor muscle in interstitial cystitis than in bacterial cystitis or normal controls. Within the urothelium and submucosa, mast cell numbers were significantly greater than in normal controls in both interstitial and bacterial cystitis. In interstitial cystitis mast cells were significantly larger within the detrusor than in the urothelium/submucosa and they appeared to degranulate predominantly within the superficial layers. Differential staining techniques, using long and short toluidine blue stains, failed to reveal statistically significant evidence of mast cell heterogeneity within the bladder wall in interstitial cystitis.

Bacterial Infections↗

Role of the immune response in interstitial cystitis.

Interstitial cystitis (IC) patients present with irritative and painful bladder symptoms and are diagnosed clinically by their symptoms, negative urine cultures, absence of other diseases, and cytoscopic findings of glomerulations and/or ulcers. The histological evaluation usually is described as nonspecific chronic inflammation. Although numerous theories of pathogenesis have been proposed, the etiology of IC is unknown. The hypothesized causes of IC include infectious, lymphovascular obstruction and neurogenic, endocrinologic, psychoneurotic, inflammatory (especially mast cells), and autoimmune pathologies. In this Review we discuss the evidence supporting a role for autoimmunity in IC and link the mast cell to the expression of the disease. Moreover, we discuss newly developed animal models that may provide insight into the etiology of IC.

Animals↗

Histamine and mucosal mast cells in interstitial cystitis.

Interstitial cystitis (IC) is a chronic inflammatory disorder of the urinary bladder of unknown aetiology and pathogenesis. The classic form (Hunner's ulcer) is characterized by high mast cell numbers in the detrusor muscle and an expansion of mucosal mast cells in the lamina propria and also in the epithelium. Such cells can be recovered in bladder washings and in the urine in single cell suspensions. We have counted the mast cells and measured the histamine in bladder washings from 16 patients with classic IC and from a control group of 15 patients with so-called early, non-ulcerative IC. The bladder washings from all patients with classic IC contained well preserved mast cells (median 2.16, range 0.5-8.6 x 10(3) cells/I) and histamine (median 14.3, range 6-66 ng/l), while only occasional mast cells and traces of histamine were found in washings from patients with non-ulcerative IC. The histamine content was strongly correlated to the number of mast cells (r = 0.87). The mean histamine content per mast cell was estimated at 7.6 +/- 0.65 (SEM) pg/cell. The high histamine content per mast cell in relation to previously published data (2.8-4.6 pg/cell) can be attributed to the mild and rapid handling of the specimens.

Adult↗

Observations on interstitial cystitis.

Interstitial cystitis is more common in young women than previously believed. Findings typical of the disease are a history of diurnal and nocturnal pollakiuria, pelvic discomfort increases with bladder distention, marked bladder tenderness on gentle palpation of the anterior later vaginal fornices, less than normal bladder capacity, and a negative urinalysis except for many epithelial cells.

Cystitis↗