Therapy Of Interstitial Cystitis Research Articles

Pigmentary Maculopathy Associated with Chronic Exposure to Pentosan Polysulfate Sodium

To describe the clinical features of a unique pigmentary maculopathy noted in the setting of chronic exposure to pentosan polysulfate sodium (PPS), a therapy for interstitial cystitis (IC). Retrospective case series. Six adult patients evaluated by a single clinician between May 1, 2015, and October 1,2017. Patients were identified by query of the electronic medical record system. Local records were reviewed, including results of the clinical examination, retinal imaging, and visual function assessment with static perimetry and electroretinography. Molecular testing assessed for known macular dystrophy and mitochondrial cytopathy genotypes. Mean best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution units), median cumulative PPS exposure, subjective nature of the associated visual disturbance, qualitative examination and imaging features, and molecular testing results. The median age at presentation was 60 years (range, 37-62 years). All patients received PPS for a diagnosis of IC, with a median cumulative exposure of 2263 g (range, 1314-2774 g), over a median duration of exposure of 186 months (range, 144-240 months). Most patients (4 of 6) reported difficulty reading as the most bothersome symptom. Mean BCVA was 0.1±0.18 logarithm of the minimum angle of resolution. On fundus examination, nearly all eyes showed subtle paracentral hyperpigmentation at the level of the retinal pigment epithelium (RPE) with a surrounding array of vitelliform-like deposits. Four eyes of 2 patients showed paracentral RPE atrophy, and no eyes demonstrated choroidal neovascularization. Multimodal retinal imaging demonstrated abnormality of the RPE generally contained in a well-delineated area in the posterior pole. None of the 4 patients who underwent molecular testing of nuclear DNA returned a pathogenic mutation. Additionally, all 6 patients showed negative results for pathogenic variants in the mitochondrial gene MTTL1. We describe a novel and possibly avoidable maculopathy associated with chronic exposure to PPS. Patients reported symptoms of difficulty reading and prolonged dark adaptation despite generally intact visual acuity and subtle funduscopic findings. Multimodal imaging and functional studies are suggestive of a primary RPE injury. Additional investigation is warranted to explore causality further.

Interleukin-33 as a Potential Therapeutic Target for Interstitial Cystitis: New Perspectives on Mast Cell Regulation.

There are many problems still unresolved by modern medicine. In the field of voiding disorders, interstitial cystitis (IC) remains a representative disease yet to be conquered. The exact pathophysiologic mechanism of IC is not understood. Although several hypotheses have been proposed, including leaky epithelium, mast cell activation, and neurogenic inflammation, no theory has been clearly established yet [1]. IC may have multiple causes and may represent a final common reaction of the bladder to multifactorial etiology. Most researchers believe that the mast cell plays a key role in the common pathophysiology of IC. Despite many efforts to clarify the etiology of IC, our knowledge is insufficient for useful insights into effective treatments [2]. The current therapeutic goal is the improvement of quality of life, and not curative treatment. It is believed that histamine, which is secreted from mast cells, causes specific symptoms of IC such as pain, hyperemia, and fibrosis. Therefore, antihistamine treatment to adjust mast cell activation is considered a scientifically robust and rational therapy for IC. However, results using antihistamines in clinical practice were disappointing. Sufficient evidence does not exist to conclusively state that antihistamines effectively regulate the activation of mast cells in the bladder [3]. In this issue of the International Neurourology Journal, we have published an article reviewing new perspectives on mast cell regulation [4]. It was confirmed in other organs that interleukin (IL) 33 can modulate allergic inflammation. IL-33 is closely related to mast cell activation, which is considered the core of IC pathogenesis. Therefore, it may be possible to regulate mast cell activation by inhibiting IL-33. Promising results have been reported in a number of studies. However, because the reaction of the anti–IL-33 could vary in different organs, we have many challenges to overcome before systemic administration of anti–IL-33 as a therapeutic agent can be implemented. Nevertheless, this is valuable work as it presents a potential therapeutic target for an incurable disease yet unconquered by modern medicine. The most important message of this review for urologists is included in the last sentence of conclusion: “co-operative research among allergologists and urologists could yield more meaningful conclusions about the pathophysiologic mechanism and treatment strategies for interstitial cystitis” [4].

GAG layer replenishment therapy for chronic forms of cystitis with intravesical glycosaminoglycans—A review

Glycosaminoglycan (GAG) layer replenishment is a cornerstone in the therapy of interstitial cystitis (IC). During the last years intravesical GAG layer replenishment has proven to be an effective treatment for overactive bladder (OAB), radiation cystitis, and recurrent urinary tract infections (UTIs). Examination of different substances available for intravesical GAG replenishment and evaluation of the evidence for the treatment of the above-mentioned conditions. We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE) database for studies on intravesical GAG replenishment. A total of 27 clinical studies remain relevant to this topic, many of them with mixed patient selection and suboptimal definition of symptom improvement/success. Two placebo controlled studies with hyaluronic acid failed to show superiority and have not been published. One active controlled randomized study has been published showing that chondroitin sulphate 0.2% has a clear benefit for OAB patients. Another study with chondroitin sulphate 2.0% failed to show statistically significant evidence, but was underpowered. A short number of randomized controlled studies confirm efficacy of intravesical GAG layer replenishment therapy. Concluded from the study background (which comprises also uncontrolled studies), so far chondroitin sulphate 0.2% is in favor for intravesical GAG layer replenishment therapy. In general, large-scale trials are urgently needed to underline the benefit of this type of therapy.

Association between response to pentosan polysulfate sodium therapy for interstitial cystitis and patient questionnaire-based treatment satisfaction

ABSTRACTObjective: To evaluate the relationship between symptom reduction and satisfaction with pentosan polysulfate sodium (PPS) therapy in subjects with interstitial cystitis (IC).Methods: A secondary analysis was conducted in 128 subjects treated with PPS 300 mg/day (US Food and Drug Administration-approved dose) from a 32-week multicenter, randomized, double-blind study of 380 subjects with IC who were treated with PPS 300 mg/day, 600 mg/day, or 900 mg/day. Self-rated outcome measures included the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and a treatment satisfaction questionnaire. Treatment responders were defined as subjects having ≥30% reduction in ICSI from baseline to study end point.Results: A reduction in IC symptoms was associated with significantly higher satisfaction with PPS (p < 0.05). Compared with nonresponders, subjects achieving a ≥30% reduction in ICSI were more likely to be pleased with PPS for IC symptoms, to have benefited from PPS for their IC symptoms, to recommend PPS for IC symptoms to others with the same condition, and to say that PPS provides better relief, based on prior experience with other IC treatments. Among all subjects at week 32, 75% said they would recommend PPS therapy for IC symptoms to others with the condition.Conclusion: Despite limitations (lack of placebo control, use of a nonvalidated instrument), this analysis demonstrated significantly increased treatment satisfaction with PPS therapy among treatment responders versus nonresponders. There was a significant positive correlation between ICSI scores and response on the treatment satisfaction questionnaire. Treatment response and patient satisfaction with treatment are important clinical considerations in the management of patients with IC.

Normalization of proliferation and paracellular permeability of bladder epithelial cells from interstitial cystitis patients by a synthetic inhibitor of antiproliferative factor

Objectives: Interstitial cystitis (IC) is a chronic disorder with bladder epithelial thinning or ulceration, pain, urinary frequency and urgency. Bladder epithelial cells from IC patients make an antiproliferative factor (APF) that inhibits cell growth, decreases tight junctions, and increases paracellular permeability. We screened inactive synthetic APF derivatives for their ability to inhibit APF, then determined the ability of an inhibitory derivative to normalize proliferation and permeability of IC cells.Methods: Normal bladder cells were pretreated with inactive APF derivatives, then incubated with active synthetic APF. IC cells were incubated with varying concentrations of D‐proline APF. Cell proliferation was determined by 3H‐thymidine incorporation. Gene expression was determined by quantitative RT‐PCR. Paracellular permeability was determined by 14C mannitol and 3H‐inulin flux on Transwell plates.Results: One of 28 inactive derivatives (D‐proline APF) blocked APF activity in normal bladder cells. D‐proline APF also significantly increased cell proliferation, increased zonula occludens‐1 and claudin 1, 4 and 8 expression, and decreased permeability of IC cells.Conclusions: D‐proline APF can normalize IC cell proliferation and paracellular permeability in vitro, making it a potential therapy for IC. Supported by NIH R01 DK52596 and the Intramural Research Program of the NCI, NIH

Patient Perceived Outcomes of Treatments Used for Interstitial Cystitis

Interstitial cystitis (IC) is a challenging disease complex. Patients' perception of their outcomes after different treatment modalities may be the best measure of therapeutic efficacy. Our study focused on a large group of women with a diagnosis of IC who reported on perceived outcomes after undergoing invasive and pharmaceutical treatments for their disease. Seven hundred fifty patients with a diagnosis of IC completed a computerized survey that queried each patient about their demographics, symptoms, concomitant diagnoses, treatments, and their perceived treatment outcomes. The patients were surveyed on therapies used to treat IC and whether they perceived their condition to be improved, not affected or having deteriorated at a mean follow-up of 6 months. Pearson chi-squared tests were used in the statistical analyses. Invasive and medical therapies were surveyed. The most commonly performed procedures were hydrodistention (61.9%), intravesical therapy (40.1%), and urethral dilatation (26.5%). Of these procedures, 24.4% to 45.3% of patients were improved by these procedures; whereas 27.0% to 49.8% felt no effect and 25.9% to 30.7% worsened. A comparison of the number of patients who improved with those who deteriorated while on medical therapy was found to be significant for all drugs (P <0.001). The majority of patients reported that medications improved their condition, perceptively. Medical therapy is perceived to be superior to invasive therapy in the treatment of IC. Medication should be considered the first line therapy for IC. Several medications showed a large percentage of patients with improvement in symptoms. These medications were calcium glycerophosphate (Prelief, AkPharma Inc, Pleasantville, NJ), phenazopyridine, and pentosan polysulfate sodium.

Beneficial effects of suplatast tosilate (IPD‐1151T) in a rat cystitis model induced by intravesical hydrochloric acid

To examine the effects of suplatast tosilate (IPD-1151T), a Th2 cytokine inhibitor recently recognized to improve the symptoms in patients with interstitial cystitis (IC), in a rat model of HCl-induced chronic cystitis, to elucidate the possible mechanisms by which the drug improves the symptoms of IC. Chronic cystitis was induced by intravesical instillation of 0.2 mL of 0.4 m HCl in female adult rats. After a once-daily oral administration of IPD-1151T (0.1-100 mg/kg) or prednisolone (5 mg/kg) for 7 days, cystometry was performed under urethane anaesthesia. The bladder from HCl-induced cystitis rats was also assessed histopathologically. On cystometrography there was frequent voiding in cystitis rats. Administration of IPD-1151T for 7 days after intravesical HCl instillation dose-dependently increased the micturition volume and intercontraction intervals. Treatment with prednisolone had similar therapeutic effects. Histological analyses in the bladder from cystitis rats revealed oedema and infiltration of inflammatory cells such as mast cells and eosinophils in the lamina propria and the transitional epithelial thickening. These histological changes and the number of mast cells and eosinophils were reduced by administration of IPD-1151T or prednisolone. The present results indicate that IPD-1151T improves bladder function and pathological changes in HCl-induced cystitis rats, as previously observed in patients with IC. The rat cystitis model induced by HCl could provide useful information for studying proposed therapies for IC which might involve T cell-dependent inflammatory responses as one of its potential pathophysiologies.

Efficacy of Interstitial Cystitis Treatments: A Review

Objective Interstitial cystitis (IC) is a chronic clinical condition known for more than a century. Its pathophysiology remains largely unclear. No universally-effective treatment exists, and many patients do not respond to available therapies. There is no evidence-based algorithm and no standard therapy for IC. The aims of this article are to review the available treatment options and to evaluate the degree of evidence regarding their clinical efficacy. Materials and Methods We reviewed English language publications on IC from January 1966 to August 2005 listed in MEDLINE, and we selected clinical studies reporting on IC treatment. For each treatment type, we give the level of evidence and the recommendation grade according to the “Oxford University Program for Evidence-based Studies”. Results Most articles were retrospective, non-randomized, uncontrolled studies with small numbers of patients. Twenty articles provided high-level evidence. Three therapies are supported by a high level of evidence: oral Cimetidine and Amitriptyline, and one intravesical agent, Dimethylsulfoxide (DMSO). Reports on surgical treatments were only open investigations. Conclusion IC treatment is complex and controversial because of the disease's unidentified, formal etiology. We proposed an evidence-based algorithm that might be helpful when counseling IC patients regarding treatment options and expectations from each therapy.

What is the value of cystoscopy with hydrodistension for interstitial cystitis?

Objectives To determine the utility of cystoscopy with hydrodistension for the diagnosis and therapy of interstitial cystitis. Cystoscopy with hydrodistension is the most commonly performed diagnostic test and procedure in patients with interstitial cystitis. Methods Eighty-four consecutive patients with interstitial cystitis (68 women and 16 men) were studied retrospectively. The patients underwent history and physical examination, urinalysis, and urine culture and filled in a voiding diary and pain urgency frequency questionnaire. Cystoscopy with hydrodistension was performed in 47 patients. Patients who had and had not undergone hydrodistension were compared. Patients who underwent hydrodistension were characterized and followed up for response. Results The mean patient age was 41 years, mean daily voided volume was 98 mL, mean number of nocturnal episodes was 3, and pain urgency frequency score was 21. Comparing patients undergoing versus not undergoing hydrodistension, pain was reported in 61% versus 25% ( P = 0.03), vaginal pain in 62% versus 32% ( P = 0.02), and dyspareunia or ejaculatory pain in 67% versus 29% ( P <0.01), respectively. All other parameters were statistically similar. Of the patients undergoing hydrodistension, 43 had follow-up and 24 (56%) reported improvement (mean duration of 2 months). Of the patients with and without improvement, no difference was found in mean age (40 versus 46 years, P = 0.20), duration of symptoms (7 versus 7 years, P = 0.92), anesthetic capacity (722 versus 721 mL, P = 0.99), or glomerulation grade ( P = 0.61), respectively. Conclusions Cystoscopy with hydrodistension provided little useful information above and beyond the history and physical examination findings. As therapy, 56% of patients reported improvement, but the duration was short lived.

534Comparative assessment of maximal bladder capacity, 0.9% NaCl VS. 0.2 M KCl before and after therapy for interstitial cystitis

534Comparative assessment of maximal bladder capacity, 0.9% NaCl VS. 0.2 M KCl before and after therapy for interstitial cystitis

How do you stretch a bladder? A survey of UK practice, a literature review, and a recommendation of a standard approach.

To assess how and why hydrodistension of the bladder is performed by UK urologists and to compare this practise with the published literature on distension. To suggest a standardised technique for hydrodistension to allow comparison of diagnostic and therapeutic studies. A questionnaire was sent to all UK consultant urologists. Questions addressed the indications for short bladder distension (SBD), details of technique, evaluation of outcome, and awareness of evidence base. The literature on bladder distension was reviewed. The majority of respondents perform SBD, principally in the diagnosis and therapy of interstitial cystitis (IC). There was considerable variation in the duration of distension, repetition of distension, the pressure used for distension, and the measurement of bladder capacity. The literature on the technique of hydrodistension is imprecise and no respondent was able to cite literature to support his or her practice. We suggest a simple, more objective technique for performing hydrodistension. SBD is widely used. There is marked variability in technique and little more than anecdotal evidence to support any particular approach. Research into the evaluation and treatment of painful bladder syndrome in general and IC in particular would be facilitated by the adoption of a standardised technique.

801 Electromotive drug administration (EMDA) of pentosan polysulfate (PPS) in the therapy of interstitial cystitis (IC)

801 Electromotive drug administration (EMDA) of pentosan polysulfate (PPS) in the therapy of interstitial cystitis (IC)

Pregnancy Outcomes following the Diagnosis of Interstitial Cystitis

Objective: To describe the outcome of pregnancy in patients treated for interstitial cystitis. Methods: Over a 4-year period, 12 patients with interstitial cystitis who had one course of intravesical dimethyl sulphoxide (DMSO) therapy for interstitial cystitis were studied. Information on the effects of the treatment-to-conception interval, symptom control during pregnancy and immediately post partum, other pregnancy events and pregnancy outcome were collected. Results: The mean age was 32 years (SD = 5.4), and 6 (50%) were nulliparous. Fifty-eight percent of the women presented with combined urinary and pain symptoms, 25% with a pain symptom only and 17% with a urinary symptom only. Eleven women had 1 course (6 doses) of DMSO therapy. Symptom relief was maintained during pregnancy in almost all the women. The mean interval from diagnosis of interstitial cystitis to the first day of the last menstrual cycle preceding all pregnancies beyond 28 weeks was 19.3 months (SD = 14.7). This interval was 6 months or less for 2 pregnancies that were terminated on account of symptoms attributable to interstitial cystitis. Thirteen healthy babies were delivered. Conclusion: Pregnancy outcomes appear good following treatment for interstitial cystitis with 1 course of intravesical DMSO.

Interstitial cystitis: a review of current concepts of aetiology, diagnosis and therapy.

Until recently, interstitial cystitis (IC) has been described as a chronic clinical syndrome of obscure aetiology and, consequently, specific treatment for the condition is lacking. IC has often been regarded as a diagnosis of exclusion in women complaining of chronic pelvic pains, frequency, dysuria, etc. and until recently most clinicians rarely considered this diagnosis in men. However, recent research efforts have begun to yield vital information on this underdiagnosed and distressing clinical condition regarding its aetiology and diagnosis and, consequently, more effective therapeutic options are now emerging. The aim of this review is to highlight these emerging concepts of the aetiology, diagnosis and innovative therapy of IC, in order to help clinicians confronted by patients with this disorder.

PILOT STUDY OF SEQUENTIAL ORAL ANTIBIOTICS FOR THE TREATMENT OF INTERSTITIAL CYSTITIS

Interstitial cystitis is a chronic disease of unknown etiology characterized by bladder pain, urgency and frequency. Although a single microbe has not been implicated as a cause of interstitial cystitis, several groups noted various organisms in the urine of some women with interstitial cystitis and some patients reported that antibiotics decrease symptoms. Consequently we performed a prospective, randomized, double-blinded, placebo controlled pilot study of sequential oral antibiotics. We randomized 50 patients with interstitial cystitis to receive 18 weeks of placebo or antibiotics, including rifampin plus a sequence of doxycycline, erythromycin, metronidazole, clindamycin, amoxicillin and ciprofloxacin for 3 weeks each. Intent to treat analysis demonstrated that 12 of 25 patients (48%) in the antibiotic and 6 of 25 (24%) in the placebo group reported overall improvement (p = 0.14), while 10 and 5, respectively, noticed improvement in pain and urgency (p = 0.22). In the antibiotic group 20 participants (80%) had adverse effects compared with 10 (40%) in the placebo group (p = 0.009). Our findings suggest that these antibiotics alone or in combination may sometimes be associated with decreased symptoms in some patients but they do not represent a major advance in therapy for interstitial cystitis.

Is there an association between vulvodynia and interstitial cystitis?

Objective: To prospectively evaluate the relationship between vulvodynia and interstitial cystitis (IC).Methods: Patients who were referred to a tertiary care clinic with vulvodynia refractory to standard therapies were evaluated for interstitial cystis (IC) via history, physical examination, and cystoscopy with hydraulic bladder dilation. Patients diagnosed with IC were offered treatment. Primary outcome measures were a change in average daily pain score based on 11-point Likert scale, and an investigator-rated clinical impression of pain at 6 months.Results: Twenty-five patients were evaluated for IC. Seventeen patients (68%) were diagnosed with IC, three patients (12%) had equivocal findings, and five patients (20%) had no evidence of IC. Therapy was initiated for the 17 patients diagnosed with IC, with a reduction in average daily pain score from 7.5 to 2.9 at 6 months. Using the investigator-rated impression of pain, 7/17 patients (41%) had significant improvement in their pain, 8/17 patients (47%) were moderately improved, and 2/18 (12%) were minimally improved.Conclusions: Sixty-eight percent of women with refractory vulvodynia were found to have IC. Therapy for IC improved pain scores at 6 months for vulvodynia patients with co-existing IC; 41% were significantly improved and 47% mod-erately improved. These findings suggest an association between vulvodynia and IC. Assessment for IC is warranted for patients with vulvodynia refractory to other therapies.

HIGH AFFINITY BINDING SITES FOR [(3) H]SUBSTANCE P IN URINARY BLADDERS OF CATS WITH INTERSTITIAL CYSTITIS

Pain is a common feature of interstitial cystitis (IC). Although the effects of IC on sensory neuron density have been investigated, its influence on substance P receptor (SPR) numbers and function are not well known. To evaluate the role of SPR in cats with IC, we measured the affinity (Kd), numbers (Bmax), and substrate specificity of binding sites for [3H]SP in urinary bladders of healthy cats and cats suffering from IC. Radioligand binding assays of cat and rat brain, normal cat bladders, and inflamed bladders from cats diagnosed with IC were conducted using [3H]SP to determine SPR affinity and numbers. Binding sites for [125I]SP were identified using autoradiography in slide-mounted frozen tissue sections, and their specificity determined with competition binding studies. In bladder homogenate binding studies, low affinity SP binding sites for [3H]SP were found both in normal and inflamed tissue, whereas high affinity binding sites were found in inflamed bladder tissue only. Based on autoradiographic studies, high affinity binding appeared to be to small blood vessels, and to be specific for substance P, a pharmacology consistent with the neurokinin-1 receptor (NK1R). Upregulation of NK1R may be part of the pathophysiology of IC, as it is in some other inflammatory diseases. If so, more specifically targeted therapies for IC may become available.

Hydroxine Therapy for Interstitial Cystitis

Hydroxine Therapy for Interstitial Cystitis

Hydroxine Therapy for Interstitial Cystitis

Hydroxine Therapy for Interstitial Cystitis

Interstitial cystitis and the gynecologist.

Interstitial cystitis (IC) is a predominantly female condition with the presenting symptoms of frequency of micturition and pain. The diagnosis is confirmed by bladder visualization at cystoscopy during filling, emptying, and redistension. The epidemiology, proposed etiologies, and current therapies for interstitial cystitis are discussed. The condition of IC is poorly understood and has no specific histological characteristics. However, there is much that can be offered to the IC sufferer to relieve or cure her symptoms. It is hoped that the recent decade of increasing research activity will be fruitful in answering questions of etiology and pathogenesis, and offering hope for new therapies and ultimately cure.