Prevalence of interstitial cystitis symptoms in a managed care population

PURPOSE: We calculated the prevalence of symptoms typically associated with interstitial cystitis (IC) in men and women in a managed care population in the Pacific Northwest. MATERIALS AND METHODS: International Classification of Diseases-9 based queries of the Kaiser Permanente Northwest, Portland, Oregon database were used to identify subjects with IC exclusion criteria, who were excluded from further analysis. A total of 10,000 questionnaires, including 5,000 for women and 5,000 for men, were mailed to subjects with codes indicating bladder symptoms and to those with none of the codes. The questionnaires included questions about the presence of IC symptoms and the O'Leary-Sant interstitial cystitis questionnaire. IC symptoms were defined in 2 ways, that is as 1) pelvic pain at least 3 months in duration plus urgency or frequency at least 3 months in duration and 2) the same criteria plus pain increasing as the bladder fills and/or pain relieved by urination. RESULTS: The prevalence of IC symptoms according to definitions 1 and 2 was 11.2% and 6.2% in women, and 4.6% and 2.3% in men, respectively. Symptoms were long-standing (duration greater than 1 year in 80% of cases) and bothersome (severity score 5 or greater in greater than 50%). Mean O'Leary-Sant interstitial cystitis questionnaire scores were 15.94 in subjects with definition 1 IC symptoms, 18.97 in those with definition 2 IC symptoms and 6.69 in those with no IC symptoms (p <0.001). Symptoms were most common and most severe in subjects previously diagnosed with IC. CONCLUSIONS: The prevalence of IC symptoms is 30 to 50-fold higher in women and 60 to 100-fold higher in men than the prevalence of a coded physician diagnosis of IC in the same population. Although these findings are not conclusive, they imply that IC may be significantly under diagnosed.     

Depressive symptoms and quality of life in patients with interstitial cystitis

PURPOSE: Previous research suggests that patients with interstitial cystitis have poorer quality of life and higher levels of depressive symptoms. However, most studies to date have been limited by the lack of standard measures to describe the experience of living with interstitial cystitis. In addition, to our knowledge no study has used a structured interview to assess depressive symptomatology. We investigated the extent of depressive symptoms and impaired quality of life in a sample of female patients with interstitial cystitis compared with healthy controls. Relationships among physician rated symptom severity, quality of life and depressive symptoms were also examined. MATERIALS AND METHODS: At a clinic visit 65 female patients previously diagnosed with interstitial cystitis and 40 age matched, healthy controls completed questionnaires on depressive symptoms (Beck Depression Inventory) and quality of life (Medical Outcomes Study 36-Item Short Form), and a structured interview on depressive symptoms (Hamilton Rating Scale for Depression) with trained interviewers. RESULTS: Patients reported compromised quality of life compared with healthy controls across various domains, including physical functioning, ability to function in one's normal role and vitality. They also had more severe depressive symptoms on the 2 depression measures. In patients, greater interstitial cystitis severity was associated with greater compromise in physical and social functioning, and mental health but not in other quality of life domains or depressive symptoms. CONCLUSIONS: A diagnosis of interstitial cystitis is related to poorer functioning in various life domains. Decrements increase with disease severity.     

Prevalence of interstitial cystitis symptoms in women: a population based study in the primary care office

PURPOSE: We estimated the prevalence of urinary symptoms related to interstitial cystitis (IC) in women in a primary care practice and confirmed in the United States the results of a Finnish population based prevalence study. MATERIALS AND METHODS: Every female patient presenting to our office for a routine office visit between January 9, 2004 and September 24, 2004 was evaluated for urinary symptoms using 2 validated surveys, namely the O'Leary-Sant (OLS) IC symptom and problem index, and the Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale. RESULTS: Of the 1,218 women in the study group 13 (1.1%) reported severe symptoms and problems (12 or greater on the OLS survey), including 7 (0.6%) who met previously established criteria for probable IC. In the same population scores on the PUF questionnaire indicated that 154 women (12.6%) likely had IC. CONCLUSIONS: Based on previously published criteria for use of the OLS survey the prevalence of urinary symptoms corresponding to probable IC in our study population (575/100,000 or 0.57%, 95% CI 150 to 1,000) was similar to the 0.45% rate previously reported. However, the results of the PUF questionnaire indicated that the prevalence of IC in women may actually be much higher (12,600/100,000 or 12.6%, 95% CI 10,700 to 14,500). We suggest that the true prevalence of IC in women may be somewhere between these 2 extremes. Further investigation of these questionnaires as screening tools for IC is warranted. IC may be more common in women than previously reported.     

Prevalence of symptoms related to interstitial cystitis in women: a population based study in Finland

PURPOSE: Interstitial cystitis is a chronic inflammatory bladder disease. Despite intensive research its prevalence, etiology, diagnosis and appropriate treatment remain elusive. We estimated the prevalence of urinary symptoms related to interstitial cystitis in women in Finland. MATERIALS AND METHODS: We randomly selected 2,000 study participants 18 to 71 years old from the Finnish population register. The prevalence of urinary symptoms was evaluated using the validated O'Leary-Sant interstitial cystitis symptom and problem index questionnaire, which was mailed to subjects. Women with high (12 or greater) symptom and problem scores, including nocturia 2 or greater, pain 2 or greater, and excluding urinary infection and pregnancy, were considered most likely to have interstitial cystitis. RESULTS: The response rate after 2 mailings was 67.2% (1,343 respondents). After further exclusions 1,331 women (66.6%) comprised the final study group. Of these 1,331 respondents 11 (0.8%) reported severe symptoms and problems (12 or greater), including 6 (0.45%) who fulfilled the criteria for probable interstitial cystitis. CONCLUSIONS: The prevalence of urinary symptoms corresponding to probable interstitial cystitis is 450/100.000 (95% confidence interval 100 to 800), which is an order of magnitude higher than previously reported.     

Efficiency of questionnaires used to screen for interstitial cystitis

PURPOSE: Questionnaires for the evaluation of interstitial cystitis are widely used, but their value in discriminating interstitial cystitis from other diagnoses among patients with urological symptoms has not been determined. We assessed the validity of 2 frequently used interstitial cystitis questionnaires-the O'Leary-Sant Symptom Index and Problem Index and the Pain, Urgency, Frequency Symptom Scale-for screening for interstitial cystitis. MATERIALS AND METHODS: The Pain, Urgency, Frequency Symptom Scale and the O'Leary-Sant Symptom Index and Problem Index were administered to the same 220 patients at a urology clinic before diagnosis. Questionnaire scores between patients with and without interstitial cystitis, as well as among diagnostic groups, were compared by parametric and nonparametric analyses. Receiver operating characteristic curves were constructed to determine the efficiency of each questionnaire in discriminating between patients with and without interstitial cystitis. RESULTS: Interstitial cystitis was distinguishable from the other diagnoses using both questionnaires (p <0.001). Separate analyses of bother and symptom scores yielded similar results. Receiver operating characteristic curves demonstrated the Pain, Urgency, Frequency Symptom Scale to be more efficient than the O'Leary-Sant Symptom Index and Problem Index in detecting interstitial cystitis in this population with an optimal cutoff value of 13 or greater. CONCLUSIONS: While the Pain, Urgency, Frequency Symptom Scale and the O'Leary-Sant Symptom Index and Problem Index questionnaires distinguish interstitial cystitis from other urinary tract pathologies, neither questionnaire demonstrates sufficient specificity to serve as the sole diagnostic indicator. These questionnaires should not be used to define interstitial cystitis, but can be used to screen patients with urinary tract symptoms to identify those who should be further examined for interstitial cystitis or to follow those who have already been diagnosed.     

Diurnal cortisol variations and symptoms in patients with interstitial cystitis

PURPOSE: Little attention has focused on systemic factors that may allow a state of chronic bladder inflammation to be established and maintained in interstitial cystitis cases. Abnormalities of the hypothalamic-pituitary-adrenal feedback system result in poorer regulation of the inflammatory response and are present in many chronic inflammatory and pain conditions, of which some have high co-morbidity with interstitial cystitis. MATERIALS AND METHODS: A total of 48 patients with interstitial cystitis and 35 healthy, age matched controls collected 24-hour urine samples and 3 days of salivary samples at 7 to 8 a.m., 4 to 5 p.m. and 8 to 9 p.m. for cortisol analysis. In addition, they completed a concurrent symptom questionnaire. Prospective symptom diaries also were completed in the month before sampling. RESULTS: Mean urinary or salivary cortisol did not differ in patients and controls. However, patients with interstitial cystitis and higher morning cortisol had significantly less pain and urgency, while those with higher urinary free cortisol reported less overall symptomatology (p <0.05). Relationships with morning cortisol were also observed when controlling for co-morbid conditions known to be affected by the hypothalamic-pituitary-adrenal axis, such as fibromyalgia, chronic fatigue and rheumatoid arthritis. Patients with morning cortisol less than 12.5 nmol./l. were 12.8 times more likely to report high urinary urgency than those with values above this cutoff. CONCLUSIONS: These findings imply that regulation of the hypothalamic-pituitary-adrenal axis may be associated with interstitial cystitis symptomatology and there may be different diurnal hypothalamic-pituitary-adrenal patterns in patients with interstitial cystitis who do and do not have co-morbid conditions. These findings may have treatment implications for patients with interstitial cystitis who have early morning cortisol deficiencies.     

Percutaneous sacral nerve root neuromodulation for intractable interstitial cystitis

PURPOSE: We evaluated the efficacy of percutaneous sacral nerve root neuromodulation in women with refractory interstitial cystitis. MATERIAL AND METHODS: We prospectively evaluated 15 consecutive women with a mean age of 62 years who had refractory interstitial cystitis to determine the efficacy of percutaneous stimulation of the S3 sacral roots. The mean duration of symptoms before evaluation was 5.2 years. All women fulfilled the National Institute of Arthritis, Diabetes and Digestive and Kidney Diseases criteria for the diagnosis of interstitial cystitis and were unresponsive to standard oral or intravesical therapy. The response to treatment was assessed using pain scores, urinary diary variables and quality of life surveys. RESULTS: Mean voided volume during treatment increased from 90 to 143 ml. (p <0.001). Mean daytime frequency and nocturia decreased from 20 to 11 and 6 to 2 times (p = 0.012 and 0.007, respectively). Mean bladder pain decreased from 8.9 to 2.4 points on a scale of 0 to 10 (p <0.001). As indicated by the Short Urinary Distress Inventory and SF-36 Health Survey, the quality of life parameters of social functioning, bodily pain and general health significantly improved during the stimulation period. Of the women 73% requested to proceed to complete sacral nerve root implantation. CONCLUSION: Women with intractable interstitial cystitis respond favorably to percutaneous sacral stimulation with significant improvement in pelvic pain, daytime frequency, nocturia, urgency and average voided volume. Permanent sacral implantation may be an effective treatment modality in refractory interstitial cystitis but further long-term evaluation is required.     

Prevalence and incidence of interstitial cystitis in a managed care population

PURPOSE: We calculated the prevalence and incidence of physician diagnosed interstitial cystitis (IC) in men and women in a managed care population in the Pacific Northwest. MATERIALS AND METHODS: A computer search of the Kaiser Permanente Northwest (Portland, Oregon) database was performed for January 1998 to May 2002. The prevalence of IC in patients 25 to 80 years old was calculated using the 4 definitions of 1) patients assigned a diagnosis of IC, 2) patients assigned a diagnosis of IC without any of the consensus IC exclusion criteria, 3) patients who had also had undergone cystoscopy and 4) patients who had specifically undergone cystoscopy with hydrodistention for IC. A second database search was performed 1 year later (May 2003) to identify incident cases of IC. RESULTS: The prevalence of IC was 197 per 100,000 women and 41 per 100,000 men for definition 1, 158 per 100,000 women and 28 per 100,000 men for definition 2, 99 per 100,000 women and 19 per 100,000 men for definition 3, and 45 per 100,000 women and 8 per 100,000 men for definition 4. Using definition 2 the 1-year incidence of IC was 21 per 100,000 women and 4 per 100,000 men. The female-to-male ratio for each estimate was 5:1. CONCLUSIONS: The prevalence and incidence of interstitial cystitis is significantly higher for women and men than previously published estimates. Men account for a higher proportion of patients with IC than has previously been recognized.     

The cysteinyl leukotriene D4 receptor antagonist montelukast for the treatment of interstitial cystitis

PURPOSE: The presence of leukotriene D4 receptors in human detrusor myocytes and increased urinary leukotriene E4 in patients with interstitial cystitis and detrusor mastocytosis imply a role for cysteinyl containing leukotrienes as proinflammatory mediators in this disease. We examined the efficacy of the cysteinyl leukotriene 1 receptor antagonist montelukast for treating patients with interstitial cystitis and detrusor mastocytosis. MATERIALS AND METHODS: Ten women in whom interstitial cystitis was diagnosed according to National Institute of Diabetes and Digestive and Kidney Diseases criteria and who also had detrusor mastocytosis with a minimum of 28 mast cells per mm.2 muscle tissue were included in this study. Patients received a single dose of montelukast daily for 3 months. The efficacy of treatment was determined by 24-hour urinary frequency, nocturia and pain using visual analog scales. RESULTS: After 1 month of montelukast treatment there was a statistically significant decrease in 24-hour urinary frequency, nocturia and pain which persisted during the 3 months of treatment. After 3 months 24-hour urinary frequency had decreased from 17.4 to 12 voidings (p = 0.009), nocturia had decreased from 4.5 to 2.8 (p = 0.019) and pain had decreased from 46.8 to 19.6 mm. on a visual analog scale (p = 0.006). No side effects were observed during treatment. CONCLUSIONS: Montelukast treatment resulted in significant improvement in urinary frequency and pain. Its efficacy for decreasing urinary frequency and pain imply a role of leukotriene receptor antagonists for managing interstitial cystitis but further placebo controlled clinical studies are needed.     

Clinical guidelines for interstitial cystitis and hypersensitive bladder syndrome

A clinical guideline and algorism for interstitial cystitis and hypersensitive bladder syndrome has been developed by a group of East Asian urologists as a revised form of the Japanese guideline for interstitial cystitis. The guideline defines interstitial cystitis (IC) as a disease of the urinary bladder diagnosed by 3 requirements; 1) a characteristic complex of lower urinary tract symptoms, 2) bladder pathology such as Hunner's ulcer and bladder bleeding after overdistension, and 3) exclusions of confusable diseases. The characteristic symptom complex is termed as hypersensitive bladder syndrome (HBS), which is defined as bladder hypersensitivity, usually associated with urinary frequency, with or without bladder pain. For the definite diagnosis of IC, cytoscopy or hydrodistension is crutial; HBS is the diagnosis when IC is suspected but not confirmed by the 3 requirements. Numerous therapeutic options are available; however, most of them lack in high level of evidence, leaving a few as recommended therapies. Etiology of IC are multifactorial; the interaction among nervous, immune and endocrine factors forms a vicious cycle, provocating and maintaining inflammatory reactions in the bladder. The inclusion and efficacy criteria for clinical trials should be standardized to enhance the clinical research for this disabling disease, which has proved to be more prevalent than previously believed.     

Role of liposome in treatment of overactive bladder and interstitial cystitis

Intravesical (local) therapy of agents has been effective in delaying or preventing recurrence of superficial bladder cancer. This route of drug administration has also shown tremendous promise in the treatment of interstitial cystitis/painful bladder syndrome (IC/PBS) and overactive bladder without systemic side effects. Liposomes are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core. They can incorporate drug molecules, both hydrophilic and hydrophobic, and show greater uptake into cells via endocytosis. Intravesical liposomes have therapeutic effects on IC/PBS patients, mainly because of their ability to form a protective lipid film on the urothelial surface. Recent studies have shown the sustained efficacy and safety of intravesical instillation of botulinum toxin formulated with liposomes (lipo-BoNT) for the treatment of refractory overactive bladder This review considers the current status of intravesical liposomes or liposomal mediated drug delivery for the treatment of IC/PBS and overactive bladder.     

Psychophysical evidence of hypersensitivity in subjects with interstitial cystitis

PURPOSE: We quantified differences in somatic and visceral sensation in healthy subjects and subjects with interstitial cystitis (IC). MATERIALS AND METHODS: A total of 13 subjects with IC and 13 healthy subjects answered psychological questionnaires and underwent psychophysical testing of thermal and pressure thresholds for sensation as well as the ischemic forearm test of pain tolerance. A subset of subjects also underwent bladder sensory testing with the determination of 3 consecutive cystometrograms. Ratings of intensity and unpleasantness were determined. RESULTS: Subjects with IC were significantly more sensitive to deep tissue measures of sensation related to pressure, ischemia and bladder than healthy subjects. Cutaneous thermal pain measures were similar in the 2 groups. Psychological measures indicated higher reactivity in subjects with IC. CONCLUSIONS: Similar to other visceral pain disorders, such as irritable bowel syndrome, hypersensitivity to somatic stimuli was noted in subjects with IC. This suggests altered central mechanisms in the processing of sensory events from the bladder.     

Quantifying symptoms in men with interstitial cystitis/prostatitis, and its correlation with potassium-sensitivity testing

OBJECTIVE: To determine whether men previously diagnosed with prostatitis also have pathology originating in the bladder. PATIENTS, SUBJECTS AND METHODS: We administered the pelvic pain and urgency/frequency (PUF) questionnaire and the potassium-sensitivity test (PST) to 50 patients with prostatitis presenting in urological and primary care, and to 14 controls. In a separate control group of 22 men, the urethra was irrigated with KCl or NaCl (11 each) before and after experimental injury of the urethral mucosa. RESULTS: All 50 patients with prostatitis had PUF scores of > or = 7; 77% were positive for the PST. All 14 controls had PUF scores of 1 or 0 and a negative PST. In the urethral irrigation study in controls, KCl but not NaCl provoked urethral pain after mucosal injury. Before injury, neither KCl nor NaCl caused symptoms. CONCLUSION: The high rate of positive PST in patients with "classic" prostatitis indicates that pathology originating in the bladder may be an important source of symptoms in most. In patients with prostatitis and female patients with interstitial cystitis, symptoms may arise not from separate disease entities but from a continuum of epithelial dysfunction and potassium cycling that may be present throughout the lower urinary tract.     

Posterior tibial nerve stimulation in patients with intractable interstitial cystitis

OBJECTIVE: To evaluate the efficacy of intermittent percutaneous posterior tibial nerve stimulation (PPTNS) in patients with refractory interstitial cystitis. PATIENTS AND METHODS: One man and 13 women (mean age 58.3 years) with suprapubic or perineal pain were enrolled in a prospective open study, in which they had 10 weekly sessions of PPTNS. Their mean duration of symptoms was 8.3 years. All patients were previously diagnosed as having interstitial cystitis according to the National Institute of Diabetes and Digestive and Kidney Diseases criteria. The response to the treatment were assessed using voiding diary, visual analogue scale diary for a pain index, and the Interstitial Cystitis Problem Index (ICPI), O'Leary/Sant Interstitial Cystitis Symptom Index (ICSI) and the 36-item short-form health survey (SF-36) quality-of-life questionnaire. RESULTS: Of the 14 patients, 13 completed the 10 weeks of treatment with no complications; 12 continued treatment for a short period after the study. There were no statistically significant changes in pain scores, voiding frequency and volumes, or in the ICPI, ICSI and SF-36 scores. However, there was an improvement in some patients, with one having complete resolution of the pain. CONCLUSION: Intermittent PPTNS in patients with refractory interstitial cystitis has no significant clinical effect over 10 weeks of treatment.     

Abnormal expression of molecular markers for bladder impermeability and differentiation in the urothelium of patients with interstitial cystitis

PURPOSE: Despite a lack of consensus concerning the etiology of interstitial cystitis (IC) the loss of impermeability and other abnormalities of the urothelium are features of the disease. In this study the distribution of proteins involved with epithelial adhesion, cellular differentiation and bladder impermeability in urothelial biopsies were explored by the immunohistochemical assessment of E-cadherin, ZO-1, uroplakin and chondroitin sulfate. MATERIALS AND METHODS: Biopsies obtained from 27 patients with IC and 7 controls were immediately fixed in formalin, immunohistochemically labeled for the described proteins and scored for protein expression, morphology and differentiation. RESULTS: Only 3 IC samples appeared completely normal, while 24 of the 27 showed an abnormality in at least 1 marker and in 6 all 4 markers were abnormal. In patients vs controls findings were abnormal for uroplakin in 13 of 27 vs 1 of 7 (p = 0.085), for E-cadherin (over expressed) in 18 of 27 vs 0 of 7 (p = 0.0021), for ZO-1 in 11 of 27 vs 0 of 7 (p = 0.046) and for chondroitin sulfate in 15 of 27 vs 0 of 7 (p = 0.0054). The morphology/polarity score significantly correlated with ZO-1 (Pearson r = 0.3935, p = 0.0423) and chondroitin sulfate (Pearson r = 0.7079, p <0.0001) expression. Chondroitin sulfate and ZO-1 showed a high correlation with each other (Pearson r = 0.5587, p = 0.0025). Uroplakin and E-cadherin expression were independent of all other markers. CONCLUSIONS: The findings reported strongly suggest abnormal differentiation in the IC bladder. The disruption of ZO-1 is similar to that reported in feline IC. Elevated E-cadherin may represent an adaptation to increased bladder permeability.