Biomarkers for patients with interstitial cystitis/bladder pain syndrome

Interstitial cystitis or bladder pain syndrome (IC/BPS) is a disease of unknown etiology manifested with bladder pain and frequency urgency symptoms. Although several pathophysiologic mechanisms have been proposed, the underlying mechanism of IC/BPS is still unclear. Accumulated evidence supports that IC/BPS is actually a spectrum of clinical phenomena that involves several different genes and environmental factors. Heterogeneous syndromes are seen in patients with IC/PBS, which suggests that the disease should be classified into different subtypes. Abnormal expressions of several bladder epithelial markers, including mast cells, epithelial differentiation proteins, cell membrane proteins, neurotransmitters, and cytokines, are present in IC/BPS. This review discusses the possible biomarkers that may play crucial roles in IC/BPS, and especially focuses on those that have the potential to be used as biomarkers for prognosis and for the determination of the best treatment for patients.     

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.     

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.     

Role of serum immunoglobulin E in patients with interstitial cystitis/bladder pain syndrome

ObjectiveThe actual pathophysiology of interstitial cystitis (IC)/bladder pain syndrome (BPS) is still uncertain. Immune or hypersensitivity mechanisms may play an important role in the pathogenesis of IC/BPS. This study was designed to investigate and analyze serum immunoglobulin E (IgE) levels in patients with IC/BPS.Materials and methodsPatients with IC/BPS who were admitted for cystoscopic hydrodistention were enrolled in this study. Blood samples were obtained to investigate their serum IgE levels. A serum IgE level more than 200 IU/mL was considered abnormal. The patients' symptoms, visual analog scale (VAS) scores, O'Leary–Sant symptom (OSS) scores, cystometric bladder capacity (CBC), maximal bladder capacity (MBC), and grading of bladder glomerulation hemorrhage during cystoscopic hydrodistention were recorded. Serum IgE levels were also investigated in women with stress urinary incontinence, who served as the control group.ResultsTwo hundred patients with IC/BPS and 35 controls were investigated. In total, 22 IC/BPS patients (11%) had abnormal serum IgE levels. No abnormal serum IgE levels were detected in the controls. The mean serum IgE level in IC/BPS patients and controls were 102.37 IU/mL ± 250.68 IU/mL and 74.21 IU/mL ± 88.62 IU/mL, respectively (p = 0.204). The VAS, OSS, CBC, MBC, and grading of glomerulations were not significantly correlated with serum IgE levels (p = 0.317, 0.587, 0.774, 0.559, and 0.309, respectively). The serum IgE levels were slightly higher in men than in women, although the difference was not significant (152.98 IU/mL ± 201.73 IU/mL vs. 94.87 IU/mL ± 262.54 IU/mL, p = 0.183).ConclusionIn this study, 11% of patients with IC/BPS had IgE level more than 200 IU/mL, but the mean serum IgE level was not higher than the controls. Aggravating factors such as food or environmental substance should be carefully investigated in IC/BPS patients with elevated serum IgE levels.     

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.     

中国江苏地区间质性膀胱炎/膀胱疼痛综合征患者现状调查

目的 了解江苏地区泌尿外科间质性膀胱炎/膀胱疼痛综合征(IC/BPS)患者的诊断及治疗现状,提高临床医师对于这一疾病的认知度.方法 2014年10月至2015年9月在江苏省13个城市28个泌尿外科进行横断面调查研究,对在调查时间内前来泌尿外科就诊的患者进行IC/BPS诊断的询问筛查,选择部分患者进行详细的问卷调查及IC/BPS相关检查.结果 参与调查共184例IC/BPS患者.53例(28.8％)为初诊,其余131例(71.2％)为复诊.主要描述症状:尿急43例(23.4％),尿频76例(41.3％),夜尿18例(9.8％),疼痛47例(25.5％).治疗方案中单一用药22例(12.0％),联合用药162例(88.0％).女性患者平均ICSI、ICPI、OABSS、VAS、QOL评分均高于男性,最大排尿量较少(P＜0.05).男性α受体阻滞剂及植物药应用较多,女性M受体阻滞剂及膀胱内治疗应用较多(P＜0.05).结论 IC/BPS严重影响生活质量,目前临床应用的检查及治疗方案与国际上有一定差异,需要提高医师对疾病的认识.     

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.