Clinical guidelines for interstitial cystitis/bladder pain syndrome

The clinical guidelines for interstitial cystitis and related symptomatic conditions were revised by updating our previous guidelines. The current guidelines define interstitial cystitis/bladder pain syndrome as a condition with chronic pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by other urinary symptoms, such as persistent urge to void or urinary frequency in the absence of confusable diseases. The characteristic symptom complex is collectively referred as hypersensitive bladder symptoms. Interstitial cystitis/bladder pain syndrome is divided into Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis and bladder pain syndrome represent interstitial cystitis/bladder pain syndrome with Hunner lesions and interstitial cystitis/bladder pain syndrome without Hunner lesions, respectively. So-called non-Hunner-type interstitial cystitis featured by glomerulations or bladder bleeding after distension is included in bladder pain syndrome. The symptoms are virtually indistinguishable between Hunner-type interstitial cystitis and bladder pain syndrome; however, Hunner-type interstitial cystitis and bladder pain syndrome should be considered as a separate entity of disorder. Histopathology totally differs between Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis is associated with severe inflammation of the urinary bladder accompanied by lymphoplasmacytic infiltration and urothelial denudation, whereas bladder pain syndrome shows little pathological changes in the bladder. Pathophysiology would also differ between Hunner-type interstitial cystitis and bladder pain syndrome, involving interaction of multiple factors, such as inflammation, autoimmunity, infection, exogenous substances, urothelial dysfunction, neural hyperactivity and extrabladder disorders. The patients should be treated differently based on the diagnosis of Hunner-type interstitial cystitis or bladder pain syndrome, which requires cystoscopy to determine the presence or absence Hunner lesions. Clinical studies are to be designed to analyze outcomes separately for Hunner-type interstitial cystitis and bladder pain syndrome.     

Symptoms of interstitial cystitis, painful bladder syndrome and similar diseases in women: a systematic review

PURPOSE: In women symptoms of interstitial cystitis are difficult to distinguish from those of painful bladder syndrome and they appear to overlap with those of urinary tract infection, chronic urethral syndrome, overactive bladder, vulvodynia and endometriosis. This has led to difficulties in formulating a case definition for interstitial cystitis, and complications in the treatment and evaluation of its impact on the lives of women. We performed a systematic literature review to determine how best to distinguish interstitial cystitis from related conditions. MATERIALS AND METHODS: We performed comprehensive literature searches using the terms diagnosis, and each of interstitial cystitis, painful bladder syndrome, urinary tract infection, overactive bladder, chronic urethral syndrome, vulvodynia and endometriosis. RESULTS: Of 2,680 screened titles 604 articles were read in full. The most commonly reported interstitial cystitis symptoms were bladder/pelvic pain, urgency, frequency and nocturia. Interstitial cystitis and painful bladder syndrome share the same cluster of symptoms. Chronic urethral syndrome is an outdated term. Self-reports regarding symptoms and effective antibiotic use can distinguish recurrent urinary tract infections from interstitial cystitis in some but not all women. Urine cultures may also be necessary. Pain distinguishes interstitial cystitis from overactive bladder and vulvar pain may distinguish vulvodynia from interstitial cystitis. Dysmenorrhea distinguishes endometriosis from interstitial cystitis, although many women have endometriosis plus interstitial cystitis. CONCLUSIONS: In terms of symptoms interstitial cystitis and painful bladder syndrome may be the same entity. Recurrent urinary tract infections may be distinguished from interstitial cystitis and painful bladder syndrome via a combination of self-report and urine culture information. Interstitial cystitis and painful bladder syndrome may be distinguished from overactive bladder, vulvodynia and endometriosis, although identifying interstitial cystitis and painful bladder syndrome in women with more than 1 of these diseases may be difficult.     

Interstitial cystitis/bladder pain syndrome: The evolving landscape,animal models and future perspectives

Interstitial cystitis/bladder pain syndrome is a debilitating condition of unknown etiology characterized by persistent pelvic pain with lower urinary tract symptoms and comprises a wide variety of potentially clinically useful phenotypes with different possible etiologies. Current clinicopathological and genomic evidence suggests that interstitial cystitis/bladder pain syndrome should be categorized by the presence or absence of Hunner lesions, rather than by clinical phenotyping based on symptomatology. The Hunner lesion subtype is a distinct inflammatory disease with proven bladder etiology characterized by epithelial denudation and enhanced immune responses frequently accompanied by clonal expansion of infiltrating B cells, with potential engagement of infection. Meanwhile, the non-Hunner lesion subtype is a non-inflammatory disorder with little evidence of bladder etiology. It is potentially associated with urothelial malfunction and neurophysiological dysfunction, and frequently presents with somatic and/or psychological symptoms, that commonly result in central nervous sensitization. Animal models of autoimmune cystitis and neurogenic sensitization might serve as disease models for the Hunner lesion and non-Hunner lesion subtypes, respectively. Here, we revisit the taxonomy of interstitial cystitis/bladder pain syndrome according to current research, and discuss its potential pathophysiology and representative animal models. Categorization of interstitial cystitis/bladder pain syndrome based on cystoscopy is mandatory to design optimized treatment and research strategies for each subtype. A tailored approach that specifically targets the characteristic inflammation and epithelial denudation for the Hunner lesion subtype, or the urothelial malfunction, sensitized/altered nervous system and psychosocial problems for the non-Hunner lesion subtype, is essential for better clinical management and research progress in this complex condition.     

Von der Endorganerkrankung zum klassifizierbaren Blasenschmerzsyndrom

Growing clinical and scientific data imply that the condition currently called interstitial cystitis is not just a mere bladder end-organ disease but that the symptoms perceived to be related to the bladder are rather one aspect of a complex pelvic pain syndrome. The term bladder pain syndrome/interstitial cystitis (BPS/IC) suggested by the European Society for the Study of IC/PBS (ESSIC) for this condition is currently the only one strictly consistent with the taxonomy guidelines of the European Association of Urology and the International Association for the Study of Pain. BPS would be diagnosed on the basis of chronic pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder, accompanied by at least one other urinary symptom such as persistent urge to void or urinary frequency. Confusable diseases as the cause of the symptoms must be excluded. Classification of BPS types might be performed according to findings at cystoscopy with hydrodistention and morphologic findings in bladder biopsies. The end-organ condition interstitial cystitis has thus become a chronic pain syndrome with a predominantly neurovisceral pathophysiology. In daily practice, therapeutic approaches aiming at both the peripheral bladder urothelium and central nervous targets should be combined. A multimodal treatment strategy, such as the combination of tricyclic antidepressants with instillation therapy, still appears reasonable and justified.     

Phenotyping of interstitial cystitis/bladder pain syndrome

Interstitial cystitis/bladder pain syndrome is a chronic, potentially debilitating condition characterized by pain perceived to be related to the bladder in conjunction with lower urinary tract symptoms, and includes a wide variety of clinical phenotypes with diverse etiologies. Currently the only clinically relevant proven phenotype of interstitial cystitis/bladder pain syndrome is the Hunner lesion. Whether the presence of Hunner lesions is a hallmark of a distinct disease cohort or a potentially transient feature of non‐Hunner lesion phenotype has been debated but remains controversial. There are few documented examples of a patient converting between the two forms. Growing clinical and basic evidence supports eliminating the Hunner lesion phenotype from the bladder pain syndrome umbrella and considering it a distinct disease. The Hunner lesion phenotype is characterized by distinct bladder histology, including subepithelial chronic inflammatory changes and epithelial denudation, and specific clinical characteristics (older onset age, severe bladder‐centric symptoms, reduced bladder capacity, and favorable response to the lesion‐targeted therapies). To define the Hunner lesion phenotype, it is necessary to develop an atlas of standardized images of cystoscopic (and, if possible, pathological) appearances of Hunner lesions. A true potential and clinically relevant phenotype of interstitial cystitis/bladder pain syndrome may be patients with non‐bladder‐centric symptoms, characterized by the affect dysregulation and somatic symptoms, and a greater bladder capacity in absence of Hunner lesions. In the present workshop, we concluded that the Hunner lesion is a valid phenotype and can reasonably be considered a disease in its own right. Assessment of bladder capacity and the extent of symptoms (bladder beyond or bladder centric) may help phenotyping of interstitial cystitis/bladder pain syndrome. Proper phenotyping is essential for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome, and for facilitating research.     

Patients With Chronic Pelvic Pain: Endometriosis or Interstitial Cystitis/Painful Bladder Syndrome?

BACKGROUND: Endometriosis and interstitial cystitis/painful bladder syndrome share similar symptoms. Interstitial cystitis was once considered rare, but it is now recognized as more common than previously thought. This review examines evidence that patients presenting with symptoms typically attributed to endometriosis or with unresolved pelvic pain after treatment for endometriosis may, in fact, have interstitial cystitis, and suggests approaches for appropriate diagnosis. METHODS: A MedLine search using "chronic pelvic pain," "endometriosis," "interstitial cystitis," and "bladder origin pain" as key words was performed for the most recent English-language articles. Additional references were obtained through cross-referencing the bibliography cited in each publication. DISCUSSION: The symptoms of endometriosis and interstitial cystitis frequently overlap, and these 2 conditions may even coexist in the same patient. In cases of unresolved endometriosis and persistent pelvic pain, patients may have interstitial cystitis. A variety of tools are available to aid in identifying interstitial cystitis. CONCLUSION: Gynecologists should be alert to the possible presence of interstitial cystitis in patients who present with chronic pelvic pain typical of endometriosis.     

Chronic pelvic pain syndrome and the overactive bladder: The inflammatory link

Although the causes of chronic prostatitis/chronic pelvic pain syndrome, painful bladder syndrome/interstitial cystitis, and overactive bladder remain unclear, inflammation may explain some of the causative and propagating features. Cytokines may play a role by recruiting inflammatory cells and ultimately in inducing symptoms. This paper reviews the role of cytokines in the pathophysiology of chronic prostatitis/chronic pelvic pain syndrome, overactive bladder, and painful bladder syndrome/interstitial cystitis.     

Review of intravesical therapies for bladder pain syndrome/interstitial cystitis

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic pain condition characterised by urinary frequency, urgency and pain or discomfort which the patient attributes to the bladder. It is a complex condition to manage and treat and requires a multi-disciplinary and multi-modal approach. As well as lifestyle and behavioural modifications, physical therapy and oral medications, intravesical treatments can be used in the treatment algorithm for BPS/IC. A number of intravesical agents are reviewed in this paper along with the available evidence for their use.     

Intravesical drug delivery for dysfunctional bladder

The bladder is a hollow organ that can be treated locally by transurethral catheter for intravesical drug instillation or cystoscopy for intravesical drug injection. With advancing technology, local organ‐specific therapy and drug delivery is of expanding interest for treating dysfunctional bladder, including interstitial cystitis/bladder pain syndrome, overactive bladder and sterile hemorrhagic cystitis after chemotherapy or pelvic radiation. Intravesical therapy has shown varying degrees of efficacy and safety in treating interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with new modalities being developed. Intravesical (regional) therapy has several advantages than oral (systemic) therapy, including high local concentration and less systemic toxicity. In recent years, intravesical delivery of biotechnological products including neurotoxins and immunosuppressive agents, and delivery platform including liposomes has shown promise for lower urinary tract symptoms. This review considers the current status of intravesical therapy in dysfunctional bladder including interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with special attention to lipid based novel drug‐delivery.     

Sympathetic nervous system and chronic bladder pain: a new tune for an old song

Chronic bladder pain (CBP) patients present with pelvic pain or discomfort during bladder filling, for at least a period of 6 months, which may be accompanied by lower urinary tract symptoms such as frequency, nocturia, and urgency. However, both the etiology of CBP and pathophysiological mechanisms are not well described. A number of clinical and basic animal model findings support involvement of sympathetic nervous system in chronic pain syndromes such as CBP. Examples include sympathetic overactivity and high plasma or urinary catecholamine levels that have a high correlation with nociceptive symptoms. In this review, we explored the current evidence in support of the involvement of sympathetic overactivity in CBP. As bladder inflammation often occurs among subgroups of CBP patients, we discuss the possible role of sympathetic nervous system in mastocytosis as well examples examples of animal models that further support the involvement of sympathetic dysfunction in CBP. As there is substantive evidence for cross-organ sensitization in the pelvis can lead to co-morbidity of genitourinary and gastrointestinal dysfunctions, we also include how sympathetic dysfunction may play a role in a number of co-morbid chronic pain syndromes.     

Interstitial cystitis,bladder pain syndrome,hypersensitive bladder,and interstitial cystitis/bladder pain syndrome – clarification of definitions and relationships

Interstitial cystitis and interstitial cystitis‐related conditions such as bladder pain syndrome and hypersensitive bladder have a similar symptomatic profile but probably different etiologies. A meaningful classification of these diseases/conditions is mandatory for clinical and investigational progress. The condition with Hunner lesions (Hunner type interstitial cystitis) is distinct from other categories in terms of histopathology, gene expression, and clinical management. Classification should clearly differentiate the presence or absence of Hunner lesions. The term covering patients as a whole should contain interstitial cystitis, since interstitial cystitis is historically a well‐known name and used for insurance reimbursement. The proposed taxonomy features an umbrella term (interstitial cystitis/bladder pain syndrome) and two subgroups, Hunner type interstitial cystitis (with Hunner lesions) and bladder pain syndrome (without Hunner lesions). Interstitial cystitis/bladder pain syndrome is convenient for initial management, and subgroups can categorize the patients for specific management. The characteristic symptom profile is to be collectively termed as hypersensitive bladder symptoms.     

Clinical phenotyping in chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis: a management strategy for urologic chronic pelvic pain syndromes

The urologic chronic pain conditions such as chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis are syndromes whose evaluation and management are controversial. Part of the difficulty in diagnosis and therapy is the heterogeneity of etiologies and symptoms. We propose a six-domain phenotype, which can classify these patients clinically and can direct the selection of therapy in the most evidence based multimodal manner. The domains are urinary, psychosocial, organ specific, infection, neurologic and tenderness of skeletal muscles. This system is flexible and responsive to new biomarkers and therapies as their utility and efficacy are proven.     

The role of a leaky epithelium and potassium in the generation of bladder symptoms in interstitial cystitis/overactive bladder, urethral syndrome, prostatitis and gynaecological chronic pelvic pain

The traditional diagnosis of interstitial cystitis (IC) only recognizes the severe form of the disease. The far more common early and intermittent phases of the disease are not perceived to be part of IC but rather are misdiagnosed as urinary tract infection, urethral syndrome, overactive bladder, chronic prostatitis, urethritis, or a type of gynecologic pelvic pain (such as endometriosis, vulvodynia, or some type of vaginitis). All of these patient groups actually suffer from the same bladder disease. This disease results from a leaky bladder epithelium and subsequent potassium leakage into the bladder interstitium that generates the symptoms of frequency, urgency, pain or incontinence in any combination. Robust scientific data now support this important concept. These data will be reviewed herein. The conclusions derived from these data substantially alter the paradigms for urology and gynecology in the generation of frequency, urgency and pelvic pain. All the above-mentioned syndromes unite into one primary disease process, lower urinary dysfunction epithelium, or LUDE disease, and not the 10 plus syndromes traditionally recognized.     

Chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis: Are they related?

Interstitial cystitis and chronic prostatitis/chronic pelvic pain syndrome are clinical syndromes characterized by pelvic pain with or without voiding symptoms such as urgency and frequency. There are many similarities in their epidemiology, adverse effect on quality of life, etiology/pathophysiology, natural history, and response to similar treatments. However, overlapping clinical definitions and similar entrance criteria for large-scale cohort studies make comparisons problematic. Newer efforts to classify pelvic pain syndromes should help in our recognition that interstitial cystitis and chronic prostatitis/chronic pelvic pain syndrome likely are not organ-specific syndromes but urogenital manifestations of regional or systemic abnormalities.     

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.     

Epidural spinal cord stimulation for interstitial cystitis

INTRODUCTION: Interstitial cystitis, a chronic inflammatory disorder of the bladder wall, is highly painful and incapacitating. Urinary frequency and urgency develop, as well as nocturia, dysuria, perineal pain and reduction of bladder capacity. The condition seems to arise from a variety of factors with multiple and diverse pathogenic mechanisms and is refractory to medical and surgical treatment. Because treatments are ineffective and recent studies have implicated an inflammatory neurogenic mechanism in the pathogenesis of interstitial cystitis, neuromodulation by epidural spinal cord stimulation has been suggested for treating patients in whom other measures have failed. CASE DESCRIPTION: A 66-year-old woman with a 9-year history of urinary incontinence, urinary urgency and suprapubic pain was diagnosed of interstitial cystitis. She was referred to our pain clinic with persistent symptoms after repeated attempts to treat the condition medically. After implantation of a cephalocaudal (retrograde) epidural spinal cord stimulator, pain decreased 80% and the improvement has been maintained with no complications. CONCLUSION: Results from this and previous reports allow us to state that retrograde epidural spinal cord stimulation seems to be a relatively non-invasive therapeutic approach for treating interstitial cystitis that is refractory to conventional treatments.     

Supratrigonal cystectomy and ileocystoplasty in management of interstitial cystitis

BACKGROUND: Interstitial cystitis is a chronic non-infectious inflammatory disease of the bladder of unknown aetiology which is characterized by irritative voiding symptoms and suprapubic pain related to bladder filling. Surgical treatment is indicated in severely symptomatic patients when medical therapies have failed, usually after a period of several years. The authors' experience with a modified technique of ileocystoplasty following supratrigonal cystectomy performed in five patients with interstitial cystitis is presented here. METHODS: A modified technique of bladder augmentation using ileum following supratrigonal bladder resection is described. RESULTS: All patients experienced relief from their symptoms. No patient had residual bladder pain and urinary frequency settled down in all. Bladder capacity was increased significantly. Three patients voided spontaneously postoperatively and two required clean intermittent self-catheterization. CONCLUSIONS: Supratrigonal cystectomy and ileocystoplasty can be a satisfactory option in refractory cases of interstitial cystitis. A simplified technique of ileal bladder construction that provides satisfactory bladder capacity is presented. Most urologists are familiar with ileal surgery, having used the ileum as a conduit after cystectomy for urinary diversion.     

Clinical presentation,videourodynamic characteristics,and treatment outcome in men with interstitial cystitis-like lower urinary tract symptoms

International Urology and Nephrology - In men, lower urinary tract symptoms (LUTS) similar to interstitial cystitis/bladder pain syndrome (IC/BPS) are difficult to diagnose, and treatment outcomes...     

Models of inflammation of the lower urinary tract

Inflammation of the lower urinary tract occurs frequently in people. The causes remain obscure, with the exception of urinary tract infection. Animal models have proven useful for investigating and assessing mechanisms underlying symptoms associated with lower urinary tract inflammation and options for suppressing these symptoms. This review will discuss various animal models of lower urinary tract inflammation, including feline spontaneous (interstitial) cystitis, neurogenic cystitis, autoimmune cystitis, cystitis induced by intravesical instillation of chemicals or bacterial products (particularly lipopolysaccharide or LPS), and prostatic inflammation initiated by transurethral instillation of bacteria. Animal models will continue to be of significant value in identifying mechanisms resulting in bladder inflammation, but the relevance of some of these models to the causes underlying clinical disease is unclear. This is primarily because of the lack of understanding of causes of these disorders in people. Comparative and translational studies are required if the full potential of findings obtained with animal models to improve prevention and treatment of lower urinary tract inflammation in people is to be realized.