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A prospective study of interstitial cystitis: results of longitudinal followup of the interstitial cystitis data base cohort. The Interstitial Cystitis Data Base Study Group.

PURPOSE: We present baseline characteristics and longitudinal profiles of symptoms in the Interstitial Cystitis Data Base study, a prospective cohort study of patients with interstitial cystitis. MATERIALS AND METHODS: A total of 637 eligible patients were entered into the study and followed for symptoms of pain, urgency and urinary frequency. Median followup was 31 months. RESULTS: More than 90% of patients were white women with a median age of 43 years. Using the overall pain-urgency-frequency score 7% of participants presented with mild, 44% with moderate and 49% with severe symptoms. Severe urgency in 41% of cases and severe 24-hour frequency in 41% were more common than severe pain in 29%. Of the patients 51% reported nighttime frequency of 2 or more voids. Median duration of interstitial cystitis symptoms was 8 years and 68% of participants were previously diagnosed with the condition. The 36% of patients who withdrew from study or were lost to followup were more likely to have had more severe symptoms at baseline. Patterns of change with time suggest initial symptom improvement due to regression to the mean, and an intervention effect associated with the increased followup and care of cohort participants. Although all symptoms fluctuated, there was no evidence of significant long-term change in overall disease severity. CONCLUSIONS: Our observations support the clinical observation that interstitial cystitis is a chronic disease and no current treatments have a significant impact on symptoms with time. These results provide a foundation for the design and performance of future clinical trials in interstitial cystitis using these end points in a similar patient population.

Adolescent↗

Treatments used in women with interstitial cystitis: the interstitial cystitis data base (ICDB) study experience. The Interstitial Cystitis Data Base Study Group.

OBJECTIVES: To evaluate the frequency and types of treatments reported at baseline in women who entered the Interstitial Cystitis Data Base (ICDB) cohort study. METHODS: From 1993 to 1997, 581 women were enrolled and followed in the ICDB. All treatments reported at study entry, including those prescribed for interstitial cystitis (IC) and concomitant medications, were reviewed. The number and types of treatments were evaluated with respect to baseline factors such as prior diagnosis of IC and symptom severity. RESULTS: One hundred five (18%) women were receiving no therapy at baseline. Single-mode therapy was reported by 195 (34%) women, and a combination of two treatments was reported by 119 (21%) women. Three or more treatments were reported in 162 (28%) women. A total of 183 different types of therapies were recorded. The five most commonly used therapies for IC symptoms were cystoscopy and hydrodistention, amitriptyline, phenazopyridine, special diet, and intravesical heparin. Because most patients entered the ICDB before the approval of oral pentosan polysulfate sodium (PPS), only 6% of women reported oral PPS use at baseline. There were statistically significant associations between the number and types of treatments and clinical center, a prior diagnosis of IC, and symptom severity. CONCLUSIONS: The diversity of IC therapies underscores the lack of understanding about the treatment of this syndrome. Further research in IC is essential to develop and to evaluate rational therapies and treatment algorithms. These algorithms should be "evidence based" and should be revised as the underlying etiology and pathophysiology of IC is delineated.

Amitriptyline↗

Experimental autoimmune cystitis: a potential murine model for ulcerative interstitial cystitis.

Interstitial cystitis is an inflammatory disease of unknown etiology. To facilitate the study of the pathophysiology of interstitial cystitis, an animal model that correlates with the clinical features of interstitial cystitis and expresses histologic features consistent with those observed in interstitial cystitis patients was developed. Various strains of mice were immunized with a syngeneic bladder homogenate to determine their susceptibility to the induction of autoimmune cystitis. Of 3 mouse strains tested, only the Balb/cAN mice reproducibly developed the clinical correlates and histological features consistent with those observed in interstitial cystitis. In a blinded pathologic review, autoreactive Balb/cAN bladders were correctly distinguished from chronic bacterial cystitis, sham treated bladders and normal control bladders. Edema, fibrosis, perivascular lymphocytic infiltrations and detrusor mast cell accumulation were apparent in 75% of the Balb/cAN mice 2 weeks after immunization and 100% at 4 weeks. These histologic features plateaued and remained stable for at least 6 months. Grossly, the immunized mouse bladders were fibrotic and contracted with a significantly (p < .05) decreased fluid capacity. On hydrodistension, increased vascular prominence and petechial hemorrhage (glomerulations) were evident. Instillation of 14C-urea demonstrated increased permeability in immunized bladders compared with controls. A cellular autoimmune basis for the cystitis is supported by adoptive transfer studies. Spleen cells from experimental mice but not controls transferred the histological features of the disease to naive mice. These studies outline the development of a new experimental autoimmune cystitis model that expresses features similar to those frequently observed in human interstitial cystitis, and may provide a model for the study of the inflammatory process associated with interstitial cystitis. Furthermore, these data suggest a possible role for cellular immune components in interstitial cystitis.

Animals↗

The diagnosis of interstitial cystitis revisited: lessons learned from the National Institutes of Health Interstitial Cystitis Database study.

PURPOSE: The lack of a precise working definition of interstitial cystitis may have resulted in the de facto use of the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) "research" definition by clinicians. We evaluated these strict criteria in light of the broader inclusion criteria for patients evaluated in the Interstitial Cystitis Database study to determine their utility in clinical practice as a useful basis for the diagnosis of interstitial cystitis. MATERIALS AND METHODS: A total of 379 women who completed screening for the Interstitial Cystitis Database before January 1, 1996 met the basic criteria of urinary frequency, urgency or pain for at least 6 months in duration without a diagnosable etiology. Of these patients 148 underwent cystoscopy and hydrodistention of the bladder as a part of the evaluation. All patients were followed for a minimum of 1 year. Comparisons were made between patients judged to have a clinical diagnosis of interstitial cystitis and those who met the NIDDK research definition of the syndrome. RESULTS: Almost 90% of patients potentially meeting NIDDK criteria are believed by experienced clinicians to have interstitial cystitis, confirming the research value of these criteria in defining a homogeneous population for study. However, strict application of NIDDK criteria would have misdiagnosed more than 60% of patients regarded by researchers as definitely or likely to have interstitial cystitis. CONCLUSIONS: The NIDDK criteria are too restrictive to be used by clinicians as the diagnostic definition of interstitial cystitis.

Cystitis, Interstitial↗

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↗

Eosinophilic cystitis: an uncommon form of cystitis.

Since 1959, 39 cases of eosinophilic cystitis have been reported in the literature. Eosinophilic cystitis is a rare form of allergic cystitis in patients who usually have a strong allergic history. It mimics other forms of intractable cystitis, such as interstitial cystitis, tuberculosis and bladder neoplasms. It is caused by various antigens that form immune complexes at the bladder level and stimulate eosinophilic infiltration. Food allergens, medications, topical agents and parasites have been implicated. The diagnosis is made by excluding all other forms of cystitis.

Adult↗

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↗

Pelvic lipomatosis with cystitis cystica, cystitis glandularis and adenocarcinoma of the bladder: first reported case.

Pelvic lipomatosis is a rare disease which may cause obstructive uropathy. It has been reported with cystitis cystica and cystitis glandularis. Cystitis cystica and cystitis glandularis have been reported previously as progressing to adenocarcinoma of the bladder. The first reported case of pelvic lipomatosis, cystitis cystica, cystitis glandularis and adenocarcinoma of the bladder is presented and the literature reviewed.

Adenocarcinoma↗

Histamine content and mast cell count of detrusor muscle in patients with interstitial cystitis and other types of chronic cystitis.

The quantitative mast cell count in the detrusor muscle, the histamine content and the degree of collagen staining material in the bladder wall have been evaluated in order to elucidate their value in distinguishing between patients with interstitial cystitis and other types of chronic cystitis. The number of mast cells in the detrusor muscle was statistically significantly increased in patients with interstitial cystitis compared with the control group (P less than 0.0001). With a proposed level of greater than 20 mast cells/sq mm of muscle tissue the diagnostic specificity was 88% and the diagnostic sensitivity 95%. The histamine content in the bladder wall was significantly increased in patients with interstitial cystitis (P less than 0.05) but not useful as a diagnostic test. The amount of collagen staining material was significantly increased in the intra- and inter-fascicular muscle tissue of the bladder in patients with interstitial cystitis (P less than 0.0005, P less than 0.001) and might be used as a support for the histological diagnosis, even in patients with uncontracted bladders.

Adult↗

[Eosinophilic cystitis and glandular-cystic cystitis as pseudotumor lesions].

OBJECTIVES: To report on two different types of cystitis presenting as pseudotumor. The differential diagnosis between the foregoing lesions and true tumors can only be established by biopsy. METHODS: We report two cases of cystitis (eosinophilic cystitis and glandular-cystic cystitis) with clinical, radiological and endoscopic features of a bladder tumor. The diagnosis, etiopathological aspects, clinical course and treatment of both types of cystitis are reviewed. RESULTS/CONCLUSIONS: Hematuria is the most frequent and most important symptom of these uncommon lesions. They present as space occupying lesions in more than 50% of the cases and have no specific diagnostic features. The diagnosis can only be made by pathological examination following TUR-biopsy.

Adult↗

Abnormal sensitivity to intravesical potassium in interstitial cystitis and radiation cystitis.

The urgency-frequency syndrome (UFS) (non-bacterial cystitis, interstitial cystitis) may well represent a heterogenous group with several etiologies. This study was based on the hypothesis that one subset of UFS patients has a leaky (to solutes) epithelium and cations such as potassium could thereby diffuse subepithelially and provoke symptoms. It was also hypothesized that normal impermeable transitional epithelium would not allow cations to diffuse across the cells during the K+ provocation test and no symptoms would be experienced. If the epithelium was permeable ("leaky"), diffusion would occur and provoke symptoms. Water or 0.4 M KCl was placed intravesically into normal volunteers and interstitial cystitis (IC) patients. Water did not provoke symptoms in either group but KCl provoked 4.5% of normals and 70% of IC patients. Differences were significant (P < 0.0001). This test provides a valuable diagnostic tool for UFS and a valuable research tool to separate epithelial permeability problems from other subsets of patients. A third group, consisting of 11 IC patients in remission on heparinoid therapy, was also tested and only 18% were provoked by KCl. Four patients with radiation cystitis were also examined and all four (100%) were provoked by the potassium.

Administration, Intravesical↗

Epithelial dysfunction in nonbacterial cystitis (interstitial cystitis).

Traditional concepts of impermeability of the bladder have centered around unique cellular tight junctions and ion pumps. However, recent data from our laboratory have shown that the bladder epithelium in animals and humans relies primarily on its surface glycosaminoglycans to maintain its impermeability. This study demonstrates the first disease associated with an epithelial dysfunction of the bladder, that is a leaky epithelium. The study consisted of 31 normal subjects and 56 individuals with interstitial cystitis. Interstitial cystitis patients were shown to have a leaky epithelium by placing a solution of concentrated urea into the bladder and measuring the absorption. The normal subjects absorbed 4.3% in 45 minutes, while the interstitial cystitis patients absorbed 25% (difference is highly significant, p less than 0.005). Interstitial cystitis patients with Hunner's ulcers (10) had a 34.5% absorption rate, while those without ulcers absorbed 22.8% (46). This difference also was highly significant (p = 0.002) and supports the concept that patients with ulcers have clinically worse disease.

Absorption↗

Tiaprofenic acid: an uncommon cause of cystitis often misdiagnosed as interstitial cystitis.

OBJECTIVE: To bring to the attention of Urologists that the medication tiaprofenic acid (Surgam, Albert-tiafen), a non-steroidal anti-inflammatory drug has been found to cause chemical cystitis. METHODS: Patients presenting between November 1994 and November 1995 with a confirmed or presumed diagnosis of interstitial cystitis and who were taking tiaprofenic acid are reported. RESULTS: Thirty-six patients presented with a confirmed or presumed diagnosis of interstitial cystitis. One woman without irritative symptoms presented with an abnormal ultrasound finding of a thickened bladder. Eight of these 37 patients were diagnosed with chemical cystitis from tiaprofenic acid. These eight patients (one man and seven women) with ages ranging between 46 and 79 (mean 67 years), were taking tiaprofenic acid from 22 to 84 months (mean 41.8 months), for the treatment of osteoarthritis. All eight patients had findings of inflammation at cystoscopy. Symptoms resolved from two to eight weeks (mean 5.3 weeks) in six out of the eight patients (one patient was asymptomatic and one is awaiting resolution two weeks after discontinuation), and persistence of bladder inflammation (as seen on cystoscopy) lingered greater than three months in two patients and five months one patient, after the medication was stopped. CONCLUSION: Symptoms of frequency, nocturia and suprapubic pain are associated with long term ingestion of tiaprofenic acid. Simple discontinuation of the drug will relieve symptoms usually within six weeks. The mechanism of inflammation is unknown.

Journal Article↗

Clinical highlights of the National Institute of Diabetes and Digestive and Kidney Diseases/Interstitial Cystitis Association scientific conference on interstitial cystitis.

In October 2000, the National Institute of Diabetes and Digestive and Kidney Diseases and the Interstitial Cystitis Association held a joint meeting in Minneapolis, Minnesota. Clinical highlights from this meeting are reviewed. The general state of interstitial cystitis from the vantage point of the clinician is discussed, as well as epidemiologic advances, new concepts in markers for interstitial cystitis, and new treatment strategies. Although there are no breakthroughs in finding a cure for this disorder, potential major changes in methods of diagnosis and new forms of therapy are in the offing.

Cystitis, Interstitial↗

Biopsy features are associated with primary symptoms in interstitial cystitis: results from the interstitial cystitis database study.

The purpose of this study was to investigate associations between bladder biopsy features and urinary symptoms for patients enrolled in the Interstitial Cystitis Database (ICDB) Study. Bladder biopsies were obtained during baseline screening in the ICDB Study and were evaluated for histopathologic features. Multivariable models for nighttime voiding frequency, urinary urgency, and pain were developed, incorporating biopsy features from the most diseased area of the bladder as predictors, adjusting for significant clinical factors, and clinical center variation. Among 204 interstitial cystitis (IC) patients providing biopsy specimens, cystoscopic pathology findings were not statistically associated (P >0.1) with primary IC symptoms, although the presence of Hunner's ulcer (n = 12) was suggestive of increased urinary frequency. Within a multivariable predictive model for nighttime voiding frequency, adjusting for age and minimum volume per void, 4 pathology features were noted: (1) mast cell count in lamina propria on tryptase stain; (2) complete loss of urothelium; (3) granulation tissue in lamina propria; and (4) vascular density in lamina propria on factor VIII (F8) stain were statistically significant (P <0.01). Similarly, in a multivariable model for urinary urgency, minimum volume, and percentage of submucosal granulation tissue remained statistically significant (P <0.01). Finally, the percentage of mucosa denuded of urothelium and the percentage of submucosal hemorrhage remained highly associated (P <0.01) with pain in a multivariable predictive model. The fact that the presence or severity of glomerulations was not selected for any of these predictive models suggests that cystoscopic findings of glomerulations are not predictive of IC symptoms. Furthermore, these results suggest an important role for certain pathologic features in the predictive modeling of IC symptoms.

Analysis of Variance↗

Metaplastic cystitis complicated with Von Brunn nests, cystitis cystica, and intestinal type of glandular metaplasia.

It is well documented that under certain stimuli the bladder epithelium can undergo metaplasia. The origin of glandular epithelium, which may be found in the bladder, is somewhat controversial. Endoscopic and histopathologic features of an eighty-one-year-old white man with proliferative metaplastic cystitis are presented. This case demonstrates that glandular differentiation was due to progressive cystitis rather than congenital intestinal rest.

Aged↗

Lupus cystitis: a possible additive risk factor for emphysematous cystitis in diabetes mellitus: discussion about one case.

Emphysematous cystitis (EC) is a rare condition in which gas-forming organisms are active in the bladder wall and lumen. Most of the cases have been described in patients suffering from diabetes mellitus due to glucosuria and subsequent anaerobic fermentation of glucose. To our knowledge this condition has never been described in association with systemic lupus erythematosus (SLE). We report here the first case of EC during the course of a chronic lupus cystitis (LC) in a woman suffering from SLE and type-I diabetes mellitus.

Anti-Bacterial Agents↗