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.     

Interstitial cystitis/bladder pain syndrome and glycosaminoglycans replacement therapy

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disease characterized by discomfort or recurrent abdominal and pelvic pains in the absence of urinary tract infections. Its symptomatology includes discomfort, increased bladder pressure, sensitivity and intense pain in the bladder and pelvic areas, increased voiding frequency and urgency, or a combination of these symptoms. For these reasons, this pathology has a very negative impact on quality of life. The etiology of IC/BPS is still not well understood and different hypotheses have been formulated, including autoimmune processes, allergic reactions, chronic bacterial infections, exposure to toxins or dietary elements, and psychosomatic factors. The finding of an effective and specific therapy for IC/BPS remains a challenge for the scientific community because of the lack of a consensus regarding the causes and the inherent difficulties in the diagnosis. The last recent hypothesis is that IC/BPS could be pathophysiologically related to a disruption of the bladder mucosa surface layer with consequent loss of glycosaminoglycans (GAGs). This class of mucopolysaccharides has hydrorepellent properties and their alteration expose the urothelium to many urinary toxic agents. It has been hypothesized that when these substances penetrate the bladder wall a chain is triggered in the submucosa. In order to improve the integrity and function of the bladder lining, GAG layer replenishment therapy is widely accepted as therapy for patients with IC/BPS who have poor or inadequate response to conventional therapy. Currently, Chondroitin sulfate (CS), heparin, hyaluronic acid (HA), and pentosan polysulphate (PPS), and combinations of two GAGs (CS and HA) are the available substances with different effectiveness rates in patients with IC/BPS. There are four different commercially available products for GAG replenishment including CS, heparin, HA and PPS. Each product has different concentrations and dosage formulations. Recently, a combination of CS and HA is the latest commercially available product with promising results.     

Diet and its role in interstitial cystitis/bladder pain syndrome (IC/BPS) and comorbid conditions

What's known on the subject? and What does the study add? Nearly 90% of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) report sensitivities to a wide variety of dietary comestibles. Current questionnaire‐based literature suggests that citrus fruits, tomatoes, vitamin C, artificial sweeteners, coffee, tea, carbonated and alcoholic beverages, and spicy foods tend to exacerbate symptoms, while calcium glycerophosphate and sodium bicarbonate tend to improve symptoms. At present we recommend employing a controlled method to determine dietary sensitivities, such as an elimination diet, in order to identify sensitivities while at the same time maintain optimal nutritional intake. We review current literature with regard to diet's effect upon IC/BPS and common comorbidities (irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, neuropathic pain, vulvodynia, and headache) with a focus upon questionnaire‐based investigations. We discuss the pathologic mechanisms that may link diet and IC/BPS related‐pain, concentrating upon specific comestibles such as acidic foods, foods high in potassium, caffeine, and alcohol.

• ? Up to 90% of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) report sensitivities to a wide variety of comestibles.
• ? Pathological mechanisms suggested to be responsible for the relationship between dietary intake and symptom exacerbation include peripheral and/or central neural upregulation, bladder epithelial dysfunction, and organ ‘cross‐talk’, amongst others.
• ? Current questionnaire‐based data suggests that citrus fruits, tomatoes, vitamin C, artificial sweeteners, coffee, tea, carbonated and alcoholic beverages, and spicy foods tend to exacerbate symptoms, while calcium glycerophosphate and sodium bicarbonate tend to improve symptoms.
• ? Specific comestible sensitivities varied between patients and may have been influenced by comorbid conditions.
• ? This suggests that a controlled method to determine dietary sensitivities, such as an elimination diet, may play an important role in patient management.

     

Similarities between interstitial cystitis/bladder pain syndrome and vulvodynia: implications for patient management

Interstitial cystitis/bladder pain syndrome (IC/BPS) and vulvodynia are chronic pain syndromes that appear to be intertwined from the perspectives of embryology, pathology and epidemiology. These associations may account for similar responses to various therapies.     

Therapeutic effects and predictive factors for successful intravesical hyaluronic acid instillation in patients with interstitial cystitis/bladder pain syndrome

ObjectiveHyaluronic acid (HA) is currently used in Taiwan as intravesical instillation for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). This study investigated the therapeutic effects of HA on IC/BPS in the Taiwanese population.Materials and methodsMen and women aged ≥18 years with documented IC/BPS were initially treated with four weekly intravesical HA instillations (treatment time, 1 month) and then with five monthly instillations (total treatment time, 6 months). Clinical assessments included the evaluation of the Visual Analog Scale (VAS) score of bladder pain, O'Leary–Sant Symptom (OSS) score, IC Symptom Index (ICSI), IC Problem Index (ICPI), functional bladder capacity (FBC), uroflowmetry parameters, and global response assessment (GRA). Therapeutic effects were compared between responders (GRA increased ≥ 2 scales) and nonresponders (GRA increased < 2). Multivariate linear analysis was used to determine predictive factor for successful treatment.ResultsA total of 64 patients (3 men and 61 women) with mean age of 49.4 years (range, 20–79) completed the study. Compared with the baseline data, VAS, ICSI, ICPI, OSS score, daytime frequency, nocturia, and FBC all improved at 1 month or 6 months after starting HA treatment. Significantly more improvements in ICSI, ICPI, OSS score, VAS, and FBC were noted in the responders than in the nonresponders at 6 months of treatment. A low-grade glomerulation was the only predictor for successful treatment response to intravesical HA treatment.ConclusionIntravesical HA administrations improved IC symptoms, decreased bladder pain, and decreased frequency after four instillations, and decreased nocturia and increased bladder capacity after completion of all nine instillations. Low-grade glomerulation predicts successful outcome.     

Clinical presentation and treatment of bladder pain syndrome/interstitial cystitis (BPS/IC) in India

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic disease characterized by pelvic pain urgency and frequency. Patients with severe symptoms lead a very miserable life. North American, European and Asian guidelines have been recently promulgated but they differ on many important issues. There is no consensus on its name, definition, investigations and management. Indian guidelines have also been developed and they give more importance to the symptoms in relation to micturition. Though initially believed to be rare or non-existent in India the situation has changed. In Indian patients the presentation is more or less same as the rest of the world but a large percentage have obstructive symptoms and unusual urinary symptoms. Anal discomfort is also common. In India the commonest investigation in all cases of lower urinary tract (LUT) dysfunction is ultrasonography of kidney ureter and bladder with measurement of the post void residual urine volume. Cystoscopy is also done in all the cases to rule out presence of tuberculosis or carcinoma in situ. Bladder pain syndrome/interstitial cystitis (BPS/IC) is not considered to be a clinical disease as it is difficult to rule out all differential diagnosis only from history. Hunner’s lesion is very rare. Cystoscopy with hydro distension, oral therapy, intravesical therapy and surgical therapy form the back bone of management. It is difficult to know which treatment is best for a given patient. A staged protocol is followed and all the treatment modalities are applied to the patients in a sequential fashion—starting from the non-invasive to more invasive. Intravesical botox has not been found to be effective and there is no experience with interstim neuromodulation.     

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.     

Dyspareunia and chronic pelvic pain in patients with interstitial cystitis/bladder pain syndrome

ObjectiveA previous study established that interstitial cystitis/bladder pain syndrome (IC/BPS) patients had significantly more dyspareunia and fear of pain than healthy controls. We evaluated the relationships between lower urinary tract symptoms and dyspareunia in IC/BPS patients.Materials and methodsA total of 156 IC/BPS female patients were included in this study. The diagnosis was made on the consensus of IC/PBS proposed by the Society for Urodynamics and Female Urology criteria in 2008. All women completed measures of pain severity (visual analog scale) and bladder symptom severity [IC Symptom Index, IC Problem Index, and the Pelvic Pain and Urinary/Frequency (PUF) scale]. Respondents were asked to recall if they experienced any sexual pain during or after sexual intercourse in the past 1 year. Cystoscopic hydrodistension during general anesthesia was performed for 5 minutes and maximal bladder capacity was also measured. Bivariate analyses were performed using chi-square and independent Student t tests.ResultsOf the women with a current sexual partner, 61% (96/156) reported dyspareunia during or after sexual intercourse. Of the 96 dyspareunia respondents, 46% (44/96) reported pain in the bladder only, 43% (41/96) in the vagina only, and 11% (11/96) in both the bladder and the vagina. Patients with dyspareunia complained of more severe urological pain (p = 0.02), a higher PUF scale score (p < 0.01), and larger anesthetic maximal bladder capacity (p = 0.04) than patients without dyspareunia. However, patients with dyspareunia at the bladder only had more severe urgency sensation (p < 0.01) but no differences in pain, PUF scale, severity of glomerulation, and maximal bladder capacity than those with dyspareunia at the vagina only.ConclusionIC/BPS women with dyspareunia have significantly more severe urological pain and a higher PUF scale score than women without dyspareunia. Physicians should consider sexual pain disorder in the management of patients with IC/BPS and use the PUF scale to evaluate not only IC-specific lower urinary tract symptoms, but also sexual pain disorder.     

Status of international consensus on interstitial cystitis/bladder pain syndrome/painful bladder syndrome: 2008 snapshot

Over the last 6 years there have been ongoing efforts around the world to standardize nomenclature, definition, and evaluation of interstitial cystitis/bladder pain syndrome/painful bladder syndrome. The convergence this year of several new projects stimulated an effort to bring together thought leaders from around the world to give a snapshot of current thinking with regard to this disorder. The Society for Urodynamics and Female Urology brought together thought leaders from Europe, Asia, and the United States to Miami, and a broad, structured discussion ensued which is the subject of this report. The most appropriate name of the disease remains an area of contention. A final “definition” of BPS/IC did garner substantial agreement among participants: An unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than 6 weeks duration, in the absence of infection or other identifiable causes. It seems that the world is moving to a presumptive diagnosis based on history and physical examination, and relying on invasive procedures for more complex cases, although this is by no means a universal opinion, being more prevalent in the United States and Asia than in Europe. It is hoped that the conference proceedings can serve as a basis for future efforts to develop formal definitions, guidelines, and best practice policies to further advancement of the field. Neurourol. Urodynam. 28:274–286, 2009. © 2009 Wiley‐Liss, Inc.     

A multidisciplinary approach to the evaluation and management of interstitial cystitis/bladder pain syndrome: an ideal model of care

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a complex syndrome that has long been treated with bladder directed therapies, which often fail to address the multiple underlying etiologies that can contribute to this disease process. This disease often involves symptoms that extend beyond the bladder and involve the pelvic floor making it crucial for clinicians to approach the patient using a multidisciplinary team. This article will discuss the underlying etiologies for IC/BPS and describe the multidisciplinary approach which we have found to be extremely successful in managing this patient population.     

A combined intravesical therapy with hyaluronic acid and chondroitin for refractory painful bladder syndrome/interstitial cystitis

The aims of this study were to evaluate the efficacy and tolerability of intravesical instillations of high-molecular-weight hyaluronic acid (HA) 1.6% and chondroitin sulfate (CS) 2.0% in patients with refractory painful bladder syndrome/interstitial cystitis (PBS/IC) and to observe their impact on Quality of Life. Twenty-three women were enrolled. They received bladder instillations with HA and CS weekly for 20 weeks and then monthly for 3 months. Mean follow-up after completion of therapy was 5 months. We observed a significant improvement in urinary symptoms on voiding diaries and Visual Analogue Scale for frequency (p = 0.045), urgency (p = 0.005), and pain (p = 0.001). The O'Leary-Sant Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index resulted in a significant improvement in both scores (p = 0.004 and 0.01, respectively). The Pelvic Pain and Urgency/Frequency Symptom Scale only showed significant improvement in the symptom score (p = 0.001). This promising experience seems to offer an additional therapeutic option in patients with refractory PBS/IC.