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| Hunner’s ulcers or “patches” are inflamed areas of the bladder wall, which may be seen on routine cystoscopic examination (arrow, left). Bladder scarring (white area, right) and radiating blood vessels are also visible
Context in source publication
Context 1
... diagnosis depended on a complex of symptoms including pain related to the bladder, frequency, and urgency with no other definitive cause. 9 10 Although cystoscopy with hydrodisten- sion may provide information on bladder abnor- malities-such as glomerulations (fig 2), mucosal tears, low anaesthetic bladder capacity, and Hun- ner's ulcers or "patches" (fig 3)-a retrospective study of 84 consecutive patients with the condition found the procedure no better than taking a history and performing a physical examination. 11 Bladder biopsy is not a mandated procedure unless gross abnormalities of the bladder wall are found. ...
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Objective:
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Background/aims:
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Objective
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Citations
... In Austria, cumulative prevalence was reported to be 306/100,000 in 2007 (Temml et al., 2007). The true incidence of the disease process is still poorly estimated due symptom overlap with other common bladder problems such as overactive bladder (OAB) and Urinary Tract Infections (UTI) (Marinkovic et al., 2009). The epidemiological cause of IC/PBS is still unknown and that partly justifies the motivation for this research. ...
... Moreover, the pain, oedema and fibrosis characteristic of the disease are a direct consequence of mast cell degranulation through sensitisation of neuronal cells via substance P mediated stimulation (Marinkovic et al., 2009). ...
Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) is a complex urological disease with no known cure yet. There are over 180 available treatment options, the effectiveness of which are variable. Scarce data exist regarding perception of treatments and Health Related Quality of Life (HRQoL) in this patient population. Herein, an epidemiologic description of the treatments used in IC/PBS and the relationship between illness perception and severity of symptoms was undertaken using an online questionnaire completed by members of the Bladder Health UK (BHUK). The O’Leary/Sant, Pelvic Urgency and Frequency (PUF), Brief Illness Perception and King Health questionnaires were used to collect data from study participants. A key finding of this work shows that irrespective of background treatments, many patients remain symptomatic with a mean ± SD O’Leary/Sant scores of 20.12 ± 9.38. Many participants were not on oral treatment. There were no significant differences between the O’Leary/Sant scores of cohorts currently taking oral medications and those who remain untreated (p=0.234). Amitriptyline was the most common medication used either alone or in combination for the treatment of the disease in the cohort. In terms of lifestyle changes, the O’Leary/Sant scores of those drinking alcohol were significantly lower than those not drinking (p≤0.05). There was marked deterioration of HRQoL of the respondents as evaluated by KHQ and BIP-Q. About 25% of the sample believed that IC/PBS had negative consequences for their daily lives while more than 75% could see no end to their symptoms. Most of the participants indicated that their disease made them worry and become emotionally unstable with a resultant decrease in quality of life. The BIP-Q items that were associated with IC/PBS severity were (Adjusted Odd Ratio (AOR) and Confidence Interval (CI)): Consequence 0.09 (0.02- 0.38); Treatment control 2.702 (1.25-5.81); Identity 0.141 (0.03-0.60) and Concern 9.36 (1.52- 57.63). Overall, this survey identified that over 80% of the participants were still symptomatic despite many being on no specific oral therapy. Participants were using non-guideline recommended treatments such as gabapentenoids, antibiotics, smooth muscle relaxants, and herbal formulae amongst others. This suggests a need to test the hypotheses as to whether such non-guideline treatments could be useful in IC/PBS using appropriately designed experimental studies. Accordingly, the cell culture work was aimed at demonstrating the potentials of medical grade Manuka honey (MH) on IC/PBS cellular model. This was done using β-hexosaminidase release assay, histamine ELISA and SDS PAGE. MH was tolerable at 2% and 4% and significantly inhibited release of beta hexosaminidase in SP, IgE and A23187 models p≤0.001, p=0.000 and p≤0.001 respectively. It also inhibited the release of histamine (p≤0.05). Likewise, MH at 4% also inhibited the release of IL-8 (p≤0.001) and GM-CSF (p=0.000) following A23187 stimulation and IL-8 (p≤0.001) and GM-CSF (p=0.000) after being challenged by Substance P (SP). Furthermore, MH attenuates the expression of Akt (p≤0.05), p38 (p≤0.05) and ERKI (p≤0.05) in SP challenged LAD2 cells. Similarly, MH suppressed the expression of ERK I and ERK II (p=0.000) in A23187 and IgE stimulated LAD2 cells. These results suggest that MH could be a novel candidate agent for the treatment for IC/PBS.
... Conservative treatment encompasses the identification of dietary triggers, behavioural therapy, physical therapy, and psychological counselling [2]. Pharmacotherapeutic treatments, such as amitriptyline, oral pentosan polysulphate sodium, and intravesical instillation of glycosaminoglycan layer replacement compounds, can be utilised depending on symptoms [8]. Minimally invasive surgical options such as bladder hydrodistension and intravesical botulinum toxin A injections both are recommended within European Association of Urology (EAU) guidelines [1], although the level of evidence underpinning these recommendations are weak. ...
... Traditionally, some surgeons offer incontinent diversion alone based on the belief that symptoms are relieved when urine is no longer stored in the bladder [8]. Conversely, others have argued that cystectomy is preferable to excise the inflamed bladder tissue, which is deemed to be the cause of the pain [10], in addition to avoiding the risk of pyocystis. ...
Context
Bladder pain syndrome/interstitial cystitis (BPS/IC) is a poorly understood chronic debilitating condition. Surgery is reserved for severe refractory cases; however, there is no consensus on patient selection or optimal approach.
Objective
To evaluate the evidence relating to the safety and efficacy of surgical interventions for treating BPS/IC.
Evidence acquisition
PubMed and Scopus databases were searched for original studies, using keywords “cystectomy”, “interstitial cystitis”, and “bladder pain syndrome”. Articles were reviewed and screened by three independent reviewers.
Evidence synthesis
A total of 450 patients were identified from 20 eligible studies: mean age was 54.5 yr and 90.2% were female. The median duration of symptoms preoperatively was 60 mo (range 9–84), with a mean follow-up of 45.5 mo. A total of 448 patients underwent surgery: subtotal cystectomy with cystoplasty (48.6%), cystectomy and orthotopic neobladder (21.9%), cystectomy and ileal conduit (11.2%), and urinary diversion only (18.3%). Symptomatic improvement occurred in 77.2%, with higher rates in the total cystectomy and orthotopic neobladder group. Thirty-one patients (6.9%) required secondary total cystectomy and/or ileal conduit diversion; 48.4% subsequently improved. Seventeen studies reported 102 complications overall (26.5%). Overall mortality was 1.3%.
Conclusions
Overall surgical intervention is associated with a 23% risk of failure to improve symptoms. Higher rates of improvement were reported in patients with total cystectomy. Interpretation should be guarded given the small patient number, multiple centres, and variable outcome measurements. There is a need for prospective randomised studies to answer questions regarding patient selection and optimal surgical approach.
Patient summary
In this review, we looked at the outcomes of surgery for treatment-refractory bladder pain syndrome/interstitial cystitis. We found overall symptom improvement in 77.2% of patients with a complication rate of 26.5%. However, there remains a need for further studies of higher quality to identify patients who will have symptom improvement and the best surgical option.
... Although it was considered to be a sterile environment for many years, the urinary tract is now considered to have its own urinary microbiome (UMB), according to recent studies [47]. Initially, researchers questioned the pathogenesis of interstitial cystitis or painful bladder syndrome (IC/PBS), which was traditionally thought to have an unknown etiology [48]. However, these painful chronic conditions responded in certain cases to antibiotic therapies [49,50]. ...
Purpose of Review
With recent advances in sequencing technologies and increasing research into the gut microbiome (GMB), studies have revealed associations between the GMB and urinary stone disease (USD). We sought to determine whether the evidence pointed towards a few specific gut bacteria or the broader GMB network is seemingly responsible for this relationship.
Recent Findings
Initially, Oxalobacter formigenes (OF) was pursued as the main link between GMB and USD given its ability to degrade oxalate in the gut. However, the latest studies consistently suggest that the entire GMB is much more likely to be involved in handling oxalate absorption and other risk factors for urinary stone formation, rather than just a few microbiota.
Summary
The GMB has complex networks that are likely involved in the pathophysiology of USD, although the causal mechanisms remain unclear. With increasing interest and research, potential modalities that act on the GMB may help to prevent incidence of USD.
... Hence, even innocuous urinary solutes such as dietary metabolites may become noxious stimuli; urinary potassium absorption or specific interactions between different components with the urothelium cause the inflammation, mast cell invasion, and activation of the submucosal nerve filaments. [44][45][46]54 In accordance with that, results of survey studies indicated that a high occurrence of dietary factor sensitivity made bladder symptoms worse in the population of patients with BPS/IC. [55][56][57][58] For instance, a study conducted by researchers from the University of South Florida revealed that nearly all (96%) of the 598 respondents indicated that certain foodstuffs made symptoms worse. ...
Although it has been proposed that NOD-like receptor protein 3 (NLRP3) inflammasome activation may have an important contribution to the onset of bladder pain syndrome/interstitial cystitis (BPS/IC), as of today there is still insufficient evidence to accept or to reject this hypothesis. However, taking into consideration that inflammasomes have been already shown as important mediators of cyclophosphamide-induced bladder inflammation and that some studies have also revealed human bladder epithelium expresses high levels of NLRP3, such a hypothesis seems to be reasonable. The purpose of this review is to discuss a scenario that NLRP3 inflammasome is a crucial player in the development of this disease. Identification of a novel mediator of bladder inflammation and pain could lead to emerging new therapeutic strategy and the first causative therapy.
... BPS/interstitial cystitis (IC) constitutes a heterogeneous chronic inflammatory condition of unknown etiology, more frequently in the 4th decade or later, affecting predominantly the female gender [25,26]. Although nearly 25% of women present a history of UTI with positive culture at presentation, subsequent urine cultures are negative [25]. ...
... Several proposed etiological factors include chronic infection, autoimmune dysfunction, neurogenic inflammation, urothelial leakage, and genetic factors [26,27]. ...
Context:
Until 2012, the urinary tract of healthy individuals was considered to be sterile. The advent of metagenomic sequencing revealed a unique urinary microbiota (UM). This paradigm shift appears to have prolific implications in the etiology of several functional lower urinary tract (LUT) disorders.
Objective:
To systematically summarize recent data on the role of UM in LUT dysfunction.
Evidence acquisition:
We performed a critical review according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. We conducted a search on PubMed/MEDLINE and SCOPUS with the following MESH terms/keywords: "Microbiome OR Microbiota AND (urinary disorder OR urinary tract symptom OR overactive bladder OR urinary incontinence OR interstitial cystitis OR chronic prostatitis)." The range of search was placed between January 2010 and April 2018, and articles with no full text available or those not written in English were excluded. All retrieved papers were first reviewed by title and abstract, yielding a total of 303 papers. Additional manuscripts, such as those referenced by reviews, were further included. Thirty-six publications were included.
Evidence synthesis:
Analysis by 16S rRNA sequence and expanded quantitative urine culture provided evidence for the presence of live bacteria in urine, nondetectable by standard culture protocols. Moreover, differences in the UM between healthy individuals and patients with LUT dysfunction were demonstrated.
Conclusions:
In the near future, urologists must consider urinary dysbiosis as a possible cause of different functional LUT disorders, with potential clinical implications in their diagnosis and treatment.
Patient summary:
Development of metagenomic sequencing revealed a unique urinary microbiota nondetectable by standard culture protocols. This systematic review summarizing recent data on the role of urinary microbiota in lower urinary tract (LUT) dysfunction supports urinary dysbiosis as a possible cause of different functional LUT disorders.
... 56 Amitriptyline decreases 5-hydroxytriptamine reuptake and also stabilizes mast cells acting as an anticholinergic and sedative. 57,58 Of note, an RCT by the Interstitial Cystitis Collaborative Research Network showed that only doses .50 mg/day seem to be effective. ...
Interstitial cystitis, presently known as bladder pain syndrome, has been recognized for over a century but is still far from being understood. Its etiology is unknown and the syndrome probably harbors different diseases. Autoimmune dysfunction, urothelial leakage, infection, central and peripheral nervous system dysfunction, genetic disease, childhood trauma/abuse, and subsequent stress response system dysregulation might be implicated. Management is slowly evolving from a solo act by the end-organ specialist to a team approach based on new typing and phenotyping of the disease. However, oral and invasive treatments are still largely aimed at the bladder and are based on currently proposed pathophysiologic mechanisms. Future research will better define the disease, permitting individualization of treatment.
... Summary of drugs, doses and common side effects[34][35][36]. May be used separately or combined in therapeutic cocktails. ...
Interstitial Cystitis/Painful Bladder Syndrome is a controversial chronic disease characterized by pain, urgency and frequency. Patients with severe symptoms have a very miserable life. There is still no international consensus on its name, definition, investigations and management. American, European and Asian guidelines have been recently framed but differ on many important issues. Presentations of IC/PBS patients are highly individual with the same or similar symptoms expressed differently. However, an important aspect of the symptoms is their relation to micturition. Since no internationally accepted standards exist for diagnosis and treatment, considerable variation is observed in the patient investigations. Investigations are divided between mandatory and optional. Sonography of kidney-ureter-bladder and urine culture are mandatory investigations as they rule out other pathologies. However, there is no consensus on important investigations such as cystoscopy. Some urologists believe painful bladder syndrome to be a clinical disease diagnosed on the basis of history and minimum investigations, while according to others cystoscopy confirms the disease by ruling out other potential causes of the symptoms and also helps in management decision-making. No standard protocol exists for treatment. All the available treatments work on a few patients and it is difficult to decide which treatment is best for a given patient. This dilemma has led to a policy of staged treatment where various treatment modalities are applied to the patient one after other, starting with less invasive and progressing to more invasive. Some treatment modalities like intravesical Botox and neuro-modulation are for patients with refractory IC/PBS only.
... This irritation may remain localized to the bladder, or it may help to cause and explain the comorbidity of other pelvic problems through its interference with the divergent autonomic nervous system in the pelvic region. 29,30 Modern laboratory techniques have resulted in studies of the somatosensory nervous systems in recent years. The neurons innervating the detrusor muscle are located in the dorsal columns (ascending neurons) and the lateral columns (descending neurons). ...
The purpose of this case series is to describe findings for patients with bladder pain syndrome (BPS) or interstitial cystitis (IC) who responded positively under chiropractic care.
Eight cases were selected retrospectively reviewed from 2 independent chiropractic clinics in Scotland. Cases were selected if patients reported bladder dysfunction problems and responded positively to chiropractic care. The cases in this report describe the range of patients affected by this condition. Each patient was treated using chiropractic methods that were specific to the individual case.
The patients selected for this case series showed positive response to chiropractic care over various lengths of time and numbers of treatments. Some of the chiropractic patients who had chronic spinal conditions had reoccurrence of bladder symptoms during an exacerbation of mechanical spinal problems.
This case series highlights that bladder and urinary problems may be associated with spinal dysfunction for some patients.
... The traditional definition of this illness is chronic sterile bladder inflammation of unknown etiology and it has not been possible to prove any causative pathogenic agent for this syndrome
[2,3]. Currently there are four major hypotheses of pathogenesis: 1) autoimmunity, 2) deficiency of the glycosaminoglycan layer causing increased bladder wall permeability, 3) neurogenic inflammation and 4) chronic infection
[4]. ...
Background
Interstitial Cystitis (IC) is a chronic inflammatory condition of the bladder with unknown etiology. The aim of this study was to characterize the microbial community present in the urine from IC female patients by 454 high throughput sequencing of the 16S variable regions V1V2 and V6. The taxonomical composition, richness and diversity of the IC microbiota were determined and compared to the microbial profile of asymptomatic healthy female (HF) urine.
Results
The composition and distribution of bacterial sequences differed between the urine microbiota of IC patients and HFs. Reduced sequence richness and diversity were found in IC patient urine, and a significant difference in the community structure of IC urine in relation to HF urine was observed. More than 90% of the IC sequence reads were identified as belonging to the bacterial genus Lactobacillus, a marked increase compared to 60% in HF urine.
Conclusion
The 16S rDNA sequence data demonstrates a shift in the composition of the bacterial community in IC urine. The reduced microbial diversity and richness is accompanied by a higher abundance of the bacterial genus Lactobacillus, compared to HF urine. This study demonstrates that high throughput sequencing analysis of urine microbiota in IC patients is a powerful tool towards a better understanding of this enigmatic disease.
... Patients with BPS often report worsening symptoms and increased pain perception after ingesting products that acidify urine. [11][12][13] A recent study addressed the role of ASICs in experimentally induced cystitis in rats treated with CYP, 14 providing the first evidence of ASIC up-regulation in the bladder during inflammation. CYP induced cystitis is a widely accepted animal model of this condition. ...
We examined the possible role of H(+) activated acid-sensing ion channels in pain perception. We characterized expression in bladder dome biopsies from patients with bladder pain syndrome and controls, in cultured human urothelium and in urothelial TEU-2 cells.
Cold cut biopsies from the bladder dome were obtained in 8 asymptomatic controls and 28 patients with bladder pain syndrome symptoms. Acid-sensing ion channel expression was analyzed by quantitative real-time polymerase chain reaction and immunofluorescence. Channel function was measured by electrophysiology.
Acid-sensing ion channel 1a, 2a and 3 mRNA was detected in the human bladder. Similar amounts of acid-sensing ion channel 1a and 3 were detected in detrusor smooth muscle while in urothelium acid-sensing ion channel 3 levels were higher than levels of acid-sensing ion channel 1a. Acid-sensing ion channel 2a mRNA levels were lower than acid-sensing ion channel 1a and 3 levels in each layer. Acid-sensing ion channel currents were measured in TEU-2 cells and in primary cultures of human urothelium. Activated acid-sensing ion channel expression was confirmed by quantitative real-time polymerase chain reaction. TEU-2 cell differentiation caused acid-sensing ion channel 2a and 3 mRNA up-regulation, and acid-sensing ion channel 1a mRNA down-regulation. Patients with bladder pain syndrome showed up-regulation of acid-sensing ion channel 2a and 3 mRNA but acid-sensing ion channel 1a remained unchanged. In contrast, transient receptor potential vanilloid 1 mRNA was down-regulated during bladder pain syndrome. All differences were statistically significant (p <0.05).
Several acid-sensing ion channel subunits are expressed in human bladder and TEU-2 cells, in which levels are regulated during urothelial differentiation. Up-regulation of acid-sensing ion channel 2a and 3 in patients with bladder pain syndrome suggests involvement in increased pain and hyperalgesia. Down-regulation of transient receptor potential vanilloid 1 mRNA might indicate that a different regulatory mechanism controls its expression in the human bladder.
