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Skin reactions to urine in patients with interstitial cystitis.

Eight of 11 patients with interstitial cystitis had positive skin reactions to patch tests with urine (delayed type IV or irritant reactions). The positive reactions were seen to tests with the patients' own urine, but also, although less frequently, to tests with foreign urine as well. Immediate reactions (type I reactions; prick tests, scratch patch tests, and 20-minute patch tests) were not observed. The clinical morphology and the histology of the positive patch tests suggest a toxic rather than an allergic reaction, although the latter could not be totally excluded. The positive skin reactions may be relevant in the pathogenesis of interstitial cystitis suggesting a mucosal hyperreactivity to some component of urine.

Aged↗

A referral center's experience with transitional cell carcinoma misdiagnosed as interstitial cystitis.

PURPOSE: There has been a recent trend to diagnose interstitial cystitis (IC) in a noninvasive way using a potassium sensitivity test, and a pelvic pain, urgency and frequency questionnaire. The concern is that significant pathology causing the bladder symptoms may be missed, such as transitional cell carcinoma. We present our experience with patients "labeled" as having IC who truly had cancer as the cause of irritative symptoms. MATERIALS AND METHODS: A retrospective review of patient records at our IC center was performed from 1998 to 2002. A total of 600 patients were seen at that time with the diagnosis of interstitial cystitis. RESULTS: Six patients (1%) previously diagnosed as having IC were found to have transitional cell carcinoma as the cause of symptoms, 4 of whom (67%) had no hematuria. Mean time from the diagnosis of IC to diagnosis of transitional cell carcinoma was 29.8 months. Irritative bladder symptoms resolved after identifying and treating the malignancy. CONCLUSIONS: Patients with irritative voiding symptoms require a thorough evaluation which may include cystoscopy, cytology and upper tract imaging. Hematuria was not a good predictor of cancer in our series. In the era before widespread use of minimally invasive means to diagnose IC (ie potassium sensitivity test, pelvic pain, urgency and frequency questionnaire) 1% of patients who were considered to have IC actually had transitional cell cancer as the cause of symptoms. One would expect that this number would increase if the criteria to diagnose IC and initiate treatment were oversimplified. Interstitial cystitis remains a diagnosis of exclusion.

Adult↗

Interstitial cystitis. When urgency and frequency mean more than routine inflammation.

Interstitial cystitis is fairly common in primary care practices and very common in urology practices. Still, it is probably underdiagnosed. Because symptoms can be confusing, patients are sometimes thought to have psychogenic problems or are treated repeatedly with antibiotics, despite the absence of evidence of bacterial infection. The key to correct diagnosis is awareness of the condition and its characteristics. In patients who have symptoms that resemble routine cystitis but normal results on urinalysis, interstitial cystitis should be considered as the working diagnosis. This is especially applicable in women, who are affected far wore often than men. Various therapies have been tried, but the cure, like the cause, remains unknown. Many patients respond to some form of therapy and may even have long-term remissions. However, arriving at the form of therapy that relieves symptoms in a given patient is often a trial-and-error process. A short-term trial of various methods is warranted initially. Ultimately, however, referral to a urologist may be necessary for definite diagnostic testing and additional therapy.

Cystitis, Interstitial↗

The surgical treatment of intractable interstitial cystitis.

Nineteen patients with severe intractable interstitial cystitis were treated surgically with either cecocystoplasty, urinary diversion with or without cystectomy, cystolysis or segmental bladder resection. Of the 6 patients who underwent an augmentation cecocystoplasty 4 were cured and 2 ultimately had urinary diversion before cure. Of the 7 patients who underwent urinary diversion with or without total cystectomy 6 were cured. In the cystolysis group the suprapubic pain was relieved either totally or partially in all 5 cases, and nocturia and urinary frequency were reduced substantially in each. However, only 1 patient was cured completely of all symptoms. The patient who underwent segmental resection of the bladder experienced only temporary symptomatic relief. Postoperative complications included pyocystis in 2 patients who had urinary diversion without cystectomy and hydroureteronephrosis in 1 patient after ureterosigmoidostomy that required multiple procedures. The place for each of these major surgical procedures in the treatment of intractable interstitial cystitis is discussed.

Adult↗

Experimental autoimmune cystitis in the Lewis rat: a potential animal model for interstitial cystitis.

To develop an autoimmune animal model for interstitial cystitis (IC), we injected rats with Freund's adjuvant (CFA) containing bladder homogenate (experimentals) or CFA alone (shams). We observed a doubling of urinary frequency in the experimental animals over the shams (P = 0.004) and histopathologic changes (venular congestion) consistent with IC. Statistically significant bladder capacity changes were not found. Mast cell (MC) number was not statistically different between experimentals and controls but the number of MCs from section to adjacent section within the same animal's bladder did vary markedly, indicating the MC counts are not a reliable measure of disease in the rat bladder. Splenocytes cultured from the experimental animals and transferred to naive syngeneic recipients were capable of transferring the urinary frequency changes and vascular congestion while splenocytes from animals which did not develop the condition were without effect. In summary, we have developed and autoimmune model for IC consistent with the clinical features of IC. The features of this model can be transferred to naive syngeneic recipients via adoptive splenocyte transfer. The model will permit us to ask and answer important questions about the pathogenesis and treatment of the human disease.

Animals↗

Coping strategies in patients with interstitial cystitis: relationships with quality of life and depression.

PURPOSE: Previous research has demonstrated that interstitial cystitis patients experience depressive symptoms and decrements to quality of life. However, to our knowledge the extent to which patients may be able to influence quality of life and depressive symptoms through coping strategies has not been investigated in this population. In a number of other chronic conditions specific coping strategies have been associated with the degree of impairment beyond disease severity. Therefore, the association of coping strategies with depressive symptoms, quality of life and self-reports of pain was assessed in patients with interstitial cystitis. MATERIALS AND METHODS: A total of 64 females with interstitial cystitis were recruited from a urology clinic at a tertiary medical center. Questionnaires assessing depression, quality of life, coping and symptom severity were completed and returned at a clinic appointment. Depression was also measured through a standardized semi-structured interview (Hamilton Rating Scale for Depression). All analyses controlled for age. RESULTS: Patients coping by greater catastrophizing reported greater impairments in various domains, including depressive symptoms, general mental health, social functioning, vitality and pain. Greater venting was associated with greater depressive symptoms and poorer mental health. Seeking instrumental social support was associated with fewer depressive symptoms. CONCLUSIONS: These findings suggest that maladaptive coping strategies are associated with higher levels of depressive symptoms and quality of life decrements in patients with this condition. Psychosocial interventions aimed at increasing adaptive coping may positively impact the female experience with interstitial cystitis.

Adaptation, Psychological↗

Sacral neuromodulation in patients with interstitial cystitis: a multicenter clinical trial.

Female patients with interstitial cystitis (IC) unresponsive to standard oral and intravesical therapy were enrolled at three clinical sites for percutaneous sacral nerve root stimulation (PNS) in a prospective, observational pilot study. Evaluation was in the form of a 3-day voiding diary completed both prior to and following the commencement of sacral nerve root stimulation. Symptoms were also assessed by the O'Leary-Sant Interstitial Cystitis Symptom and Problem Indices (ICSI and ICPI). Baseline and test stimulation values for voiding diary parameters and O'Leary-Sant scores were compared to determine treatment efficacy. A total of 33 patients were enrolled. Statistically significant improvements were seen in frequency, pain, average voided volume and maximum voided volume. Significant improvements were also seen in ICSI and ICPI scores. Subacute PNS appears to be effective in reducing symptom severity and increasing voided volumes in patients with IC previously unresponsive to standard therapy.

Adult↗

Interstitial cystitis is associated with intraurothelial Tamm-Horsfall protein.

A defective barrier between the urine and urothelium has been suggested as an etiology for interstitial cystitis. With immunohistochemical techniques we assayed the bladder biopsies of 14 interstitial cystitis patients and 10 normal controls for intraurothelial Tamm-Horsfall protein to assess indirectly the in vivo permeability of the urothelium. Eight pathological controls, including bladder biopsies from 3 patients with inflammation owing to infection or catheterization and biopsies of 5 transitional cell carcinomas of the bladder, also were assayed. Superficial intraurothelial Tamm-Horsfall protein was identified in the biopsies from 10 of 14 interstitial cystitis patients (71 per cent) but only 1 of 10 controls (10 per cent) (p less than 0.01). Tamm-Horsfall protein was not identified in biopsies from the pathological controls. In 6 of 7 cases when more than 1 biopsy was available for analysis the findings were identical in each specimen. There was a direct correlation between the density of detrusor mast cells and the demonstration of intraurothelial Tamm-Horsfall protein. Seven of the 9 evaluable interstitial cystitis patients with intraurothelial Tamm-Horsfall protein but only 1 of 4 without intraurothelial Tamm-Horsfall protein experienced a favorable response to intravesicle oxychlorosene sodium (p greater than 0.05). These data suggest that abnormal permeability of the urothelium is associated with and a possible cause of interstitial cystitis and that the demonstration of intraurothelial Tamm-Horsfall protein in bladder biopsy specimens may prove to be useful as a diagnostic test for interstitial cystitis.

Administration, Intravesical↗

[The study of diagnosis and treatment of interstitial cystitis].

OBJECTIVE: To discuss the diagnosis and treatment interstitial cystitis (IC). METHODS: The clinical date of 10 cases of IC (all women) were analyzed. Their age ranged from 31 to 63 years, with a mean of 41 years. Their courses ranged from 1.5 to 7 years, with a mean of 3.4 years. The symptom criteria of the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) was met for IC and no patients had Hunner's ulcer. Potassium sensitivity tests (PST) were performed in all cases. Eight were positive. The O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) was used as treatment outcome measures. ICSI score was from 9 to 20 (mean, 14 +/- 4) at baseline. All the patients were treated with hydrodistention initially. Efficacy was evaluated at 1 month after hydrodistention. The patients who failed to respond to the treatment and recurrence after the treatment were treated by oral or intravesical therapy. RESULTS: The 10 cases were followed up for 3 to 26 months (mean, 7.8 months) after hydrodistention. Five patients obtained symptom relief. Among them, symptom significantly relieved or disappeared in 2, with the score decreased > 7; symptom partially relieved in 3, with the score decreased > 3. Five cases failed to respond to the treatment. Two cases had recurrence 3 and 6 months after the treatment. The effective rate was 50%. The ICSI score was decreased to 11 +/- 6 at 1 month (t = 4.394, P < 0.05) after the treatment. Those who failed to respond or recurrence after hydrodistention were treated by other methods. Two case were treated with oral Pentosan Polysulfate, effective. Three cases were treated with amitriptylin, 2 effective. Three cases were treated with intravesical Dimethyl sulfoxide plus heparin plus dexamethasone, all effective. CONCLUSIONS: The diagnosis of IC should meet the symptom criteria of the NIDDK. PST has significant high positive rate in IC patient, which can be used not only for diagnosis but also for instruction. There are a lot of strategies in the management of patients with IC. Hydrodistention is the first choice.

Adult↗

Future research needs for the definition/diagnosis of interstitial cystitis.

In Workshop 8 at the International Conference on Interstitial Cystitis (Kyoto March 2003, future research needs for the definition/diagnosis of interstitial cystitis (IC) were discussed by the participants. To structure discussions a study proposal was used. This workshop decided that research should focus on identifying and validating classification criteria for the diagnosis of IC. This might well be done in a (multi-centre) study with a control group of urge-frequency patients without pain (OAB?). However, before doing so standards should be defined as on how to perform and interpret vaginal examination, urodynamic investigation, cystoscopy under anesthesia, potassium sensitivity test, and histopathology in these patients.

Biomedical Research↗

Incidence of Helicobacter pylori in patients with interstitial cystitis.

OBJECTIVE: Chronic gastritis has compelling similarities to interstitial cystitis (IC). It is characterised by chronic pain in a tubular organ. Histologically, epithelial damage, inflammatory response in the lamina propria and epithelial ulcerations are seen. An infective cause was rarely considered until the emergence of Helicobacter pylori over the past 15 years. We have had experience of patients with bladder pain and irritability reporting improvement with antihistamines. It has also been reported that IC symptoms improved dramatically after treatment for H. pylori infection. Previous studies have determined the incidence of H. pylori antibodies in women with IC but we examined bladder material histologically and performed the Campylobacter-like organism (CLO) test on the biopsy specimens. MATERIALS AND METHODS: A prospective controlled study was performed. Patients with urinary symptoms fulfilling the National Institute of Diabetes and Digestive and Kidney Diseases criteria for IC underwent GA cystoscopy at which the macroscopic appearance of the bladder was noted and biopsies were taken. The biopsy material underwent histological examination and CLO test. Control patients who were undergoing cystoscopy for reasons other than investigation of IC also had biopsy taken and the CLO test was performed on these specimens. RESULTS: Five of 15 patients with symptoms and signs of IC had a positive CLO test. Three of 15 patients of the control group had a positive CLO test. With the 2-sided chi(2) test there was no statistical difference between the 2 groups. CONCLUSION: Our small prospective control study does not support the hypothesis that H. pylori is an important component in the pathogenesis of interstitial cystitis.

Cystitis, Interstitial↗

Interstitial cystitis in persistent posthysterectomy chronic pelvic pain.

OBJECTIVES: Hysterectomies may be performed unnecessarily in women with chronic pelvic pain if the diagnosis of interstitial cystitis is not considered. The objectives of this study were to investigate the prevalence of interstitial cystitis in patients with posthysterectomy chronic pelvic pain and to evaluate the efficacy of various therapies for interstitial cystitis. METHODS: A study was performed of 111 patients with chronic pelvic pain whose pain persisted after hysterectomy. Patients were screened with the Pelvic Pain and Urgency/Frequency symptom scale, and underwent Potassium Sensitivity Testing. Patients were treated with dietary changes alone or in combination with cystoscopic hydrodistention or oral pentosan polysulfate, or both of these, for 3 to 6 months. RESULTS: Of the 111 patients enrolled, 79% (n=88) were diagnosed with bladder dysfunction consistent with interstitial cystitis. For patients treated with dietary modification alone (n=33), the mean score on the Pelvic Pain and Urgency/Frequency questionnaire improved 15.4%, from 13.18 at baseline to 11.15 at follow-up. For patients treated with pentosan polysulfate or cystoscopic hydrodistention, or both, plus diet changes (n=78), Pelvic Pain and Urgency/Frequency scores improved 34.2%, from 15.01 to 9.87. CONCLUSION: In this study, nonsurgical treatment for interstitial cystitis resulted in a marked improvement in symptoms that had not improved with surgery. Without determining the origin of bladder pain, gynecologists should not proceed to hysterectomy in patients with chronic pelvic pain.

Chronic Disease↗

Long-term outcome of patients with interstitial cystitis treated with low dose cyclosporine A.

PURPOSE: We evaluated patients with interstitial cystitis who had been on cyclosporine A treatment for at least a year. Symptom improvement on micturition charts and subjective expression of bladder pain were recorded. Side effects and safety of medication were evaluated. MATERIALS AND METHODS: A total of 23 patients (20 females and 3 males) fulfilling National Institute for Diabetes and Digestive and Kidney Diseases criteria of interstitial cystitis were included in this study. Age of patients at followup was 65.7 +/- 7.6 years (mean +/- SD). Mean followup was 60.8 +/- 35.7 months. Before starting cyclosporine A treatment multiple first line therapies had been tried without clinical help. RESULTS: The number of voidings in 24 hours was 20.8 +/- 6.3 before treatment. After a year of cyclosporine A treatment it was decreased to 10.2 +/- 3.8 (p < 0.001). Maximal bladder capacity increased from 161.8 +/- 74.6 to 360.7 +/- 99.3 ml in a year (p < 0.001). Mean voided volume increased from 101.4 +/- 42.7 to 246.4 +/- 97.9 ml (p < 0.001). The effect was maintained throughout followup. Of 23 total patients 20 reported no bladder pain on cyclosporine A treatment and 11 patients stopped treatment due to a good clinical effect. In 9 patients symptoms recurred within months but disappeared again after cyclosporine A treatment was restarted. Side effects of medication were infrequent. CONCLUSIONS: Cyclosporine A treatment was safe and effective in treating interstitial cystitis. The achieved therapeutic effect was maintained in the long term. Cessation of medication led to recurrence of symptoms in most cases.

Aged↗

Pelvic floor myofascial trigger points: manual therapy for interstitial cystitis and the urgency-frequency syndrome.

PURPOSE: The effectiveness of manual physical therapy was evaluated in patients with interstitial cystitis and the urethral syndrome, that is urgency-frequency with or without pelvic pain. The rationale was based on the hypothesis that pelvic floor myofascial trigger points are not only a source of pain and voiding symptoms, but also a trigger for neurogenic bladder inflammation via antidromic reflexes. MATERIALS AND METHODS: From September 1995 to November 2000, 45 women and 7 men, including 10 with interstitial cystitis and 42 with the urgency-frequency syndrome, underwent manual physical therapy to the pelvic floor for 1 to 2 visits weekly for 8 to 12 weeks. Results were determined by patient completed symptom score sheets indicating the rate of improvement according to outcome parameters, including 25% to 50%-mild, 51% to 75%-moderate, 76% to 99%-marked and 100%-complete resolution. In 10 cases these subjective results were confirmed by measuring resting pelvic floor tension by electromyography before and after the treatment course. RESULTS: Of the 42 patients with the urgency-frequency syndrome with or without pain 35 (83%) had moderate to marked improvement or complete resolution, while 7 of the 10 (70%) with interstitial cystitis had moderate to marked improvement. The mean duration of symptoms before treatment in those with interstitial cystitis and the urgency-frequency syndrome was 14 (median 12) and 6 years (median 2.5), respectively. In patients with no symptoms or brief, low intensity flares mean followup was 1.5 years. In 10 patients who underwent electromyography mean resting pelvic floor tension decreased from 9.73 to 3.61 microV., which was a 65% improvement. CONCLUSIONS: Pelvic floor manual therapy for decreasing pelvic floor hypertonus effectively ameliorates the symptoms of the urgency/frequency syndrome and interstitial cystitis.

Adult↗

Discovery of morphological subgroups that correlate with severity of symptoms in interstitial cystitis: a proposed biopsy classification system.

PURPOSE: We identified morphologically distinct subgroups in interstitial cystitis using cluster analysis and investigated the associations between cluster membership and urinary symptoms. MATERIALS AND METHODS: Of 637 patients enrolled in the Interstitial Cystitis Data Base Study 203 (32%) provided bladder biopsies at baseline screening, representing the focus of this analysis. A cluster analysis algorithm implemented in SAS PROC CLUSTER using standardized distances to measure the dissimilarity of each pair of patients with respect to select histopathological features was used to construct subgroups of these patients. Multivariate regression models for baseline nighttime and 24-hour voiding frequency, urinary urgency and pain were developed, incorporating indicator variables for cluster membership as predictors. Longitudinal urinary symptom profiles during 3 years of followup were also compared among the morphology clusters. RESULTS: Three morphology clusters were identified, corresponding to unique pathological groupings. In cluster C2 7 patients showed multiple pathological features of parenchymal damage, including several inflammatory features. In cluster C1 17 patients was characterized by complete denudation of the urothelium and variable edema. In cluster C0 in 179 patients none of the pathological features were present above the specified thresholds for C2. Cluster membership was significantly associated with baseline nighttime and 24-hour frequency (p <0.001, and with urinary urgency (p = 0.03). These significant increases in baseline symptom severity among clusters from C0 to C1 to C2 persisted throughout the 3 years of followup. CONCLUSIONS: These results suggest an important role for histopathological features in the predictive modeling of interstitial cystitis symptoms.

Adult↗

Interstitial cystitis: early diagnosis, pathology, and treatment.

In a retrospective review, 52 patients with interstitial cystitis have been studied. Patients with persistent lower tract irritative symptoms, repeatedly sterile urine, and negative urine cytology must be suspected of having interstitial cystitis, and a diagnosis of urethral syndrome in such patients is highly questionable until cystoscopy under anesthesia has been performed. We believe that the finding of multiple petechia-like hemorrhages (glomerulations) on the second distention of the bladder is the hallmark of interstitial cystitis, and that a reduced bladder capacity and a Hunner's ulcer represent a different (classic) stage of this disease. In all stages, the characteristic histologic finidng is submucosal edema and vasodilation. The presence of eosinophils and mast cells is variable, and even in the classic disease the muscularis often appears to be normal. Immuno fluorescent studies and laboratory tests, including the fluorescent antinuclear antibody test (FANA), have not helped us to diagnose (or investigate) interstitial cystitis. Bladder instillations with a 0.4 per cent solution of oxychlorosene sodium (Clorpactin WCS-90) have provided remarkable relief for many patients with this disease, particulary those with the classic form.

Adult↗

Incidence of physician-diagnosed interstitial cystitis in Olmsted County: a community-based study.

OBJECTIVE: To obtain community-based information about the incidence of interstitial cystitis, a chronic disabling condition of the bladder where knowledge is limited because there are no definitive diagnostic criteria. PATIENTS AND METHODS: All residents of Olmsted County, MN, USA who had received a physician-assigned diagnosis of interstitial cystitis between 1976 and 1996 were identified through the resources of the Rochester Epidemiology Project. The clinical findings at diagnosis and during the follow-up were ascertained from the community medical records for each study subject. RESULTS: In all, 16 women and four men received a diagnosis of interstitial cystitis during the study period. The overall age- and sex-adjusted (95% confidence interval) incidence rate was 1.1 (0.6-1.5) per 100 000 population. The age-adjusted incidence rates were 1.6 per 100 000 in women and 0.6 per 100 000 in men (P = 0.04). The median (range) age at initial diagnosis was 44.5 (27-76) years in women and 71.5 (23-79) years in men (P = 0.26). The median number of episodes of care-seeking for symptoms before the diagnosis was one for women and 4.5 for men (P = 0.03). The median duration from the onset of symptoms until the first diagnosis was 0.06 and 2.2 years in women and men, respectively (P = 0.2). CONCLUSIONS: These findings suggest that the incidence of interstitial cystitis in the community is extremely low. Although the gender difference may be real, the trend toward a later diagnosis in men than in women suggests a potential for missed diagnosis in men. This might explain some of the gender difference in the incidence of interstitial cystitis in men and women.

Adult↗

Gynecologic presentation of interstitial cystitis as detected by intravesical potassium sensitivity.

OBJECTIVE: To document the initial clinical diagnoses, determine the prevalence of urinary symptoms, and test for intravesical potassium sensitivity in gynecologic patients with chronic pelvic pain. METHODS: Gynecologists at three United States medical centers administered the Potassium Sensitivity Test to consecutive unselected pelvic pain patients. Before testing, each patient was given an initial clinical diagnosis based on the patient's chief symptomatic complaint(s) and surveyed for urologic symptoms. RESULTS: Of 134 patients, 114 (85%) had positive potassium sensitivity. Positive potassium sensitivity rates were similar across all three sites and all clinical diagnoses including endometriosis, vulvodynia (vulvar vestibulitis), and pelvic pain. A total of 75% of the subjects reported urologic symptoms, but only 2.9% received an initial diagnosis of interstitial cystitis. CONCLUSION: A significant majority of gynecologic patients presenting with pelvic pain have a positive Potassium Sensitivity Test, indicating their pain may have a bladder component (interstitial cystitis). Interstitial cystitis deserves greater consideration in the differential diagnosis of chronic pelvic pain.

Administration, Intravesical↗